Scholars@Duke
Xunrong Luo

Xunrong Luo

Boyce Haller Distinguished Professor in Nephrology
Medicine, Nephrology
xunrong.luo@duke.edu
DUMC Box 103015, Durham, NC 27710
2 Genome Court, Durham, NC 27710

Selected Publications

Murine kidney transplant outcome is best measured by transdermal glomerular filtration rate.

Journal Article Am J Transplant · December 2024 Mouse kidney transplantation provides a powerful preclinical model for the study of kidney transplant alloimmunity. However, accurate measurement of graft function is difficult because of the inaccuracy of traditional surrogate markers serum creatinine and ... Full text Link to item Cite

Research Highlights

Journal Article Transplantation · October 2024 Full text Cite

Advancing mouse models for transplantation research.

Journal Article Am J Transplant · August 2024 Mouse models have been instrumental in understanding mechanisms of transplant rejection and tolerance, but cross-study reproducibility and translation of experimental findings into effective clinical therapies are issues of concern. The Mouse Models in Tra ... Full text Link to item Cite

Negative Vaccination Strategies for Promotion of Transplant Tolerance.

Journal Article Transplantation · August 1, 2024 Organ transplantation requires the use of immunosuppressive medications that lack antigen specificity, have many adverse side effects, and fail to induce immunological tolerance to the graft. The safe induction of tolerance to allogeneic tissue without com ... Full text Link to item Cite

Research Highlights

Journal Article Transplantation · August 2024 Full text Cite

Phase-changing citrate macromolecule combats oxidative pancreatic islet damage, enables islet engraftment and function in the omentum.

Journal Article Sci Adv · June 7, 2024 Clinical outcomes for total-pancreatectomy followed by intraportal islet autotransplantation (TP-IAT) to treat chronic pancreatitis (CP) are suboptimal due to pancreas inflammation, oxidative stress during islet isolation, and harsh engraftment conditions ... Full text Link to item Cite

Research Highlights

Journal Article Transplantation · June 1, 2024 Full text Cite

Research Highlights

Journal Article Transplantation · May 2024 Full text Cite

AXL inhibition suppresses early allograft monocyte-to-macrophage differentiation and prolongs allograft survival.

Conference JCI Insight · March 8, 2024 Innate immune cells are important in the initiation and potentiation of alloimmunity in transplantation. Immediately upon organ anastomosis and reperfusion, recipient monocytes enter the graft from circulation and differentiate to inflammatory macrophages ... Full text Link to item Cite

Novel Approaches to Immunomodulation for Solid Organ Transplantation.

Journal Article Annu Rev Med · January 29, 2024 Despite significant advances in the field of transplantation in the past two decades, current clinically available therapeutic options for immunomodulation remain fairly limited. The advent of calcineurin inhibitor-based immunosuppression has led to signif ... Full text Link to item Cite

The T-cell environment: may the regulatory force be with you.

Journal Article Kidney Int · January 2024 In the study by Sasaki et al. in this issue, the authors studied infusions of ex vivo-expanded regulatory T cells in a highly clinically relevant nonhuman primate kidney transplant model. This commentary will aim to discuss the use of regulatory T cells in ... Full text Link to item Cite

Research Highlights

Journal Article Transplantation · January 1, 2024 Full text Cite

Advancing mouse models for transplantation research

Journal Article AMERICAN JOURNAL OF TRANSPLANTATION · 2024 Full text Cite

Innate Immune Responses in Transplant Immunity

Journal Article Current Transplantation Reports · December 1, 2023 Purpose of Review: Despite a significant decrease in the rate of acute rejection, long-term solid organ allotransplant success is limited by chronic rejection. Transplant research has historically focused on adaptive immune responses. However, there is a g ... Full text Cite

Micronano Titanium Accelerates Mesenchymal Stem Cells Aging through the Activation of Senescence-Associated Secretory Phenotype.

Journal Article ACS Nano · November 28, 2023 Stem cell senescence is one of the most representative events of organism aging and is responsible for many physiological abnormalities and disorders. In the scenario of orthopedic disease treatment, stem cell aging may affect the implantation outcome and ... Full text Link to item Cite

Research Highlights

Journal Article Transplantation · November 2023 Full text Cite

Standardization and Interpretation of RNA-sequencing for Transplantation.

Journal Article Transplantation · October 1, 2023 RNA-sequencing (RNA-seq) is a technique to determine the order of nucleotides in an RNA segment. Modern sequencing platforms simultaneously sequence millions of RNA molecules. Advances in bioinformatics have allowed us to collect, store, analyze, and disse ... Full text Link to item Cite

Research Highlights

Journal Article Transplantation · September 1, 2023 Full text Cite

Research Highlights.

Journal Article Transplantation · July 1, 2023 Full text Link to item Cite

Research Highlights

Journal Article Transplantation · March 1, 2023 Full text Cite

Research Highlights

Journal Article Transplantation · January 1, 2023 Full text Cite

Transcriptional responses define dysregulated immune activation in Hepatitis C (HCV)-naïve recipients of HCV-infected donor kidneys.

Journal Article PLoS One · 2023 Renal transplantation from hepatitis C (HCV) nucleic acid amplification test-positive (NAAT-positive) donors to uninfected recipients has greatly increased the organ donation pool. However, there is concern for adverse outcomes in these recipients due to d ... Full text Link to item Cite

Research Highlights

Journal Article Transplantation · November 1, 2022 Full text Cite

Blocking CCL8-CCR8-Mediated Early Allograft Inflammation Improves Kidney Transplant Function.

Journal Article J Am Soc Nephrol · October 2022 BACKGROUND: In kidney transplantation, early allograft inflammation impairs long-term allograft function. However, precise mediators of early kidney allograft inflammation are unclear, making it challenging to design therapeutic interventions. METHODS: We ... Full text Open Access Link to item Cite

Research Highlights

Journal Article Transplantation · September 1, 2022 Full text Cite

Research Highlights

Journal Article Transplantation · May 1, 2022 Full text Cite

Research Highlights

Journal Article Transplantation · March 1, 2022 Full text Cite

Research Highlights

Journal Article Transplantation · January 1, 2022 Full text Cite

Joining Forces in Basic Science: ITS Meeting 2.0.

Journal Article Transpl Int · 2022 The second International Transplant Science (ITS) meeting jointly organized by the European Society for Organ Transplantation (ESOT), the American Society of Transplantation (AST), and The Transplantation Society (TTS) took place in May 2022 in one of Euro ... Full text Link to item Cite

A Worldwide Survey of Activities and Practices in Clinical Islet of Langerhans Transplantation.

Journal Article Transpl Int · 2022 A global online survey was administered to 69 islet transplantation programs, covering 84 centers and 5 networks. The survey addressed questions on program organization and activity in the 2000-2020 period, including impact on activity of national health c ... Full text Link to item Cite

Research Highlights

Journal Article Transplantation · November 1, 2021 Full text Cite

Research Highlights

Journal Article Transplantation · September 1, 2021 Full text Cite

Research Highlights

Journal Article Transplantation · July 1, 2021 Full text Cite

Bone marrow-derived AXL tyrosine kinase promotes mitogenic crosstalk and cardiac allograft vasculopathy.

Journal Article J Heart Lung Transplant · June 2021 Cardiac Allograft Vasculopathy (CAV) is a leading contributor to late transplant rejection. Although implicated, the mechanisms by which bone marrow-derived cells promote CAV remain unclear. Emerging evidence implicates the cell surface receptor tyrosine k ... Full text Link to item Cite

Phase 3 trial of human islet-after-kidney transplantation in type 1 diabetes.

Journal Article Am J Transplant · April 2021 Allogeneic islet transplant offers a minimally invasive option for β cell replacement in the treatment of type 1 diabetes (T1D). The CIT consortium trial of purified human pancreatic islets (PHPI) in patients with T1D after kidney transplant (CIT06), a Nat ... Full text Link to item Cite

Research Highlights

Journal Article Transplantation · March 1, 2021 Full text Cite

Acute murine cytomegalovirus disrupts established transplantation tolerance and causes recipient allo-sensitization.

Journal Article Am J Transplant · February 2021 We have previously shown that acute cytomegalovirus (CMV) infection disrupts the induction of transplantation tolerance. However, what impact acute CMV infection would have on the maintenance of established tolerance and on subsequent recipient allo-sensit ... Full text Open Access Link to item Cite

Dissecting the human kidney allograft transcriptome: single-cell RNA sequencing.

Journal Article Curr Opin Organ Transplant · February 1, 2021 PURPOSE OF REVIEW: Single-cell RNA sequencing (scRNA-seq) has provided opportunities to interrogate kidney allografts at a hitherto unavailable molecular level of resolution. Understanding of this technology is essential to better appreciate the relevant b ... Full text Link to item Cite

Apoptotic Donor Cells in Transplantation.

Journal Article Front Immunol · 2021 Despite significant advances in prevention and treatment of transplant rejection with immunosuppressive medications, we continue to face challenges of long-term graft survival, detrimental medication side effects to both the recipient and transplanted orga ... Full text Link to item Cite

Research Highlights.

Journal Article Transplantation · January 1, 2021 Full text Link to item Cite

Cellular Therapies in Solid Organ Allotransplantation: Promise and Pitfalls.

Journal Article Front Immunol · 2021 Donor specific transfusions have been the basis of tolerance inducing protocols since Peter Medawar showed that it was experimentally feasible in the 1950s. Though trials of cellular therapies have become increasingly common in solid organ transplantation, ... Full text Link to item Cite

Single cell transcriptomics of mouse kidney transplants reveals a myeloid cell pathway for transplant rejection.

Journal Article JCI Insight · October 15, 2020 Myeloid cells are increasingly recognized as major players in transplant rejection. Here, we used a murine kidney transplantation model and single cell transcriptomics to dissect the contribution of myeloid cell subsets and their potential signaling pathwa ... Full text Open Access Link to item Cite

Donor apoptotic cell-based therapy for effective inhibition of donor-specific memory T and B cells to promote long-term allograft survival in allosensitized recipients.

Journal Article Am J Transplant · October 2020 Allosensitization constitutes a major barrier in transplantation. Preexisting donor-reactive memory T and B cells and preformed donor-specific antibodies (DSAs) have all been implicated in accelerated allograft rejection in sensitized recipients. Here, we ... Full text Open Access Link to item Cite

MCMV Dissemination from Latently-Infected Allografts Following Transplantation into Pre-Tolerized Recipients.

Journal Article Pathogens · July 26, 2020 Transplantation tolerance is achieved when recipients are unresponsive to donor alloantigen yet mobilize against third-party antigens, including virus. After transplantation, cytomegalovirus (CMV) reactivation in latently-infected transplants reduces allog ... Full text Link to item Cite

Murine cytomegalovirus dissemination but not reactivation in donor-positive/recipient-negative allogeneic kidney transplantation can be effectively prevented by transplant immune tolerance.

Journal Article Kidney Int · July 2020 Cytomegalovirus (CMV) reactivation from latently infected donor organs post-transplantation and its dissemination cause significant comorbidities in transplant recipients. Transplant-induced inflammation combined with chronic immunosuppression has been tho ... Full text Open Access Link to item Cite

Research Highlights

Journal Article Transplantation · July 2020 Full text Cite

Rejection of xenogeneic porcine islets in humanized mice is characterized by graft-infiltrating Th17 cells and activated B cells.

Journal Article Am J Transplant · June 2020 Xenogeneic porcine islet transplantation is a promising potential therapy for type 1 diabetes (T1D). Understanding human immune responses against porcine islets is crucial for the design of optimal immunomodulatory regimens for effective control of xenogen ... Full text Link to item Cite

Research Highlights

Journal Article Transplantation · March 1, 2020 Full text Cite

Monocytes prime autoreactive T cells after myocardial infarction.

Journal Article Am J Physiol Heart Circ Physiol · January 1, 2020 In humans, loss of central tolerance for the cardiac self-antigen α-myosin heavy chain (α-MHC) leads to circulation of cardiac autoreactive T cells and renders the heart susceptible to autoimmune attack after acute myocardial infarction (MI). MI triggers p ... Full text Link to item Cite

Research Highlights

Journal Article Transplantation · January 1, 2020 Full text Cite

Innate Functions of Dendritic Cell Subsets in Cardiac Allograft Tolerance.

Journal Article Front Immunol · 2020 Survival rates after heart transplant have significantly improved over the last decade. Nevertheless, long-term allograft viability after 10 years remains poor and the sequelae of transplant-associated immunosuppression increases morbidity. Although severa ... Full text Link to item Cite

Nanoparticle Platforms for Antigen-Specific Immune Tolerance.

Journal Article Front Immunol · 2020 Innovative approaches in nanoparticle design have facilitated the creation of new formulations of nanoparticles that are capable of selectively calibrating the immune response. These nanomaterials may be engineered to interact with specific cellular and mo ... Full text Link to item Cite

Confounding Virus in Mouse Facilities.

Journal Article Am J Transplant · December 2019 Full text Link to item Cite

The role of human CD46 in early xenoislet engraftment in a dual transplant model.

Journal Article Xenotransplantation · November 2019 BACKGROUND: Membrane cofactor protein CD46 attenuates the complement cascade by facilitating cleavage of C3b and C4b. In solid organ xenotransplantation, organs expressing CD46 have been shown to resist hyperacute rejection. However, the incremental value ... Full text Link to item Cite

Impact of infection on transplantation tolerance.

Journal Article Immunol Rev · November 2019 Allograft tolerance is the ultimate goal of organ transplantation. Current strategies for tolerance induction mainly focus on inhibiting alloreactive T cells while promoting regulatory immune cells. Pathogenic infections may have direct impact on both effe ... Full text Link to item Cite

Research Highlights

Journal Article Transplantation · November 1, 2019 Full text Cite

Research Highlights

Journal Article Transplantation · September 1, 2019 Full text Cite

Long-term tolerance of islet allografts in nonhuman primates induced by apoptotic donor leukocytes.

Journal Article Nat Commun · August 2, 2019 Immune tolerance to allografts has been pursued for decades as an important goal in transplantation. Administration of apoptotic donor splenocytes effectively induces antigen-specific tolerance to allografts in murine studies. Here we show that two peritra ... Full text Link to item Cite

Optimizing PLG nanoparticle-peptide delivery platforms for transplantation tolerance using an allogeneic skin transplant model.

Journal Article Biomaterials · July 2019 A robust regimen for inducing allogeneic transplantation tolerance involves pre-emptive recipient treatment with donor splenocytes (SP) rendered apoptotic by 1-ethyl-3-(3'-dimethylaminopropyl)-carbodiimide(ECDI) treatment. However, such a regimen is limite ... Full text Link to item Cite

Emerging approaches and technologies in transplantation: the potential game changers.

Journal Article Cell Mol Immunol · April 2019 Newly emerging technologies are rapidly changing conventional approaches to organ transplantation. In the modern era, the key challenges to transplantation include (1) how to best individualize and possibly eliminate the need for life-long immunosuppressio ... Full text Open Access Link to item Cite

Receptor tyrosine kinase MerTK suppresses an allogenic type I IFN response to promote transplant tolerance.

Journal Article Am J Transplant · March 2019 Featured Publication Recipient infusion of donor apoptotic cells is an emerging strategy for inducing robust transplantation tolerance. Daily clearance of billions of self-apoptotic cells relies on homeostatic engagement of phagocytic receptors, in particular, receptors of the ... Full text Link to item Cite

Phase-changing antioxidant scaffold shows promise for omentum islet transplantation: A non-human primate case study

Conference Transactions of the Annual Meeting of the Society for Biomaterials and the Annual International Biomaterials Symposium · January 1, 2019 Statement of Purpose: Pancreatic islet transplant is a promising clinically-used therapy for type I diabetic and post-total pancreatectomy pancreatitis patients. Islets are transplanted in a minimally invasive procedure via the hepatic portal vein. However ... Cite

Procedure-related and medical complications in and after intraportal islet transplantation

Chapter · January 1, 2019 Performed surgically or percutaneously, intraportal islet transplantation involves infusion of islet cells within the main portal vein or its tributaries. Percutaneous injection of islet cells is the most common method of intraportal islet transplantation ... Full text Cite

Acute and chronic phagocyte determinants of cardiac allograft vasculopathy.

Journal Article Semin Immunopathol · November 2018 Featured Publication Post-transplant immunosuppression has reduced the incidence of T cell-mediated acute rejection, yet long-term cardiac graft survival rates remain a challenge. An important determinant of chronic solid organ allograft complication is accelerated vascular di ... Full text Link to item Cite

Apoptotic cell-based therapies for promoting transplantation tolerance.

Journal Article Curr Opin Organ Transplant · October 2018 Featured Publication PURPOSE OF REVIEW: This article is aimed to provide readers with an updated review on the applicability, efficacy, and challenges of employing donor apoptotic cell-based therapies to promote transplantation tolerance in various experimental and clinical se ... Full text Link to item Cite

Murine CMV induces type 1 IFN that impairs differentiation of MDSCs critical for transplantation tolerance.

Journal Article Blood Adv · March 27, 2018 Featured Publication Clinical tolerance without immunosuppression has now been achieved for organ transplantation, and its scope will likely continue to expand. In this context, a previously understudied and now increasingly relevant area is how microbial infections might affe ... Full text Link to item Cite

Biomimetic nanoparticles for transplantation tolerance.

Journal Article Curr Opin Organ Transplant · February 2018 Featured Publication PURPOSE OF REVIEW: The current review aims to provide a current landscape and future trends of biomimetic nanoparticles which have the potential to revolutionize the field of transplantation in the next decade. RECENT FINDINGS: Currently, the inability to ... Full text Link to item Cite

The outstanding questions in transplantation: It's about time….

Journal Article Am J Transplant · January 2018 Featured Publication Full text Link to item Cite

Harnessing Apoptotic Cells for Transplantation Tolerance: Current Status and Future Perspectives.

Journal Article Curr Transplant Rep · December 2017 PURPOSE OF REVIEW: The use of donor apoptotic cells is an emerging therapy for inducing transplantation tolerance. In this review, we will discuss current understanding of mechanisms of this approach, as well as crucial aspects necessary for successful tra ... Full text Link to item Cite

Efferocytosis and outside-in signaling by cardiac phagocytes. Links to repair, cellular programming, and intercellular crosstalk in heart

Journal Article Frontiers in Immunology · November 1, 2017 Featured Publication Phagocytic sensing and engulfment of dying cells and extracellular bodies initiate an intracellular signaling cascade within the phagocyte that can polarize cellular function and promote communication with neighboring non-phagocytes. Accumulating evidence ... Full text Cite

MerTK Cleavage on Resident Cardiac Macrophages Compromises Repair After Myocardial Ischemia Reperfusion Injury.

Journal Article Circ Res · September 29, 2017 Featured Publication RATIONALE: Clinical benefits of reperfusion after myocardial infarction are offset by maladaptive innate immune cell function, and therapeutic interventions are lacking. OBJECTIVE: We sought to test the significance of phagocytic clearance by resident and ... Full text Link to item Cite

Personalized Peptide Arrays for Detection of HLA Alloantibodies in Organ Transplantation.

Journal Article J Vis Exp · September 6, 2017 Featured Publication In organ transplantation, the function and longevity of the graft critically rely on the success of controlling immunological rejection reactivity against human leukocyte antigens (HLA). Histocompatibility guidelines are based on laboratory tests of anti-H ... Full text Link to item Cite

Differential Role of B Cells and IL-17 Versus IFN-γ During Early and Late Rejection of Pig Islet Xenografts in Mice.

Journal Article Transplantation · August 2017 Featured Publication BACKGROUND: Xenogeneic islet transplantation is an emerging therapeutic option for diabetic patients. However, immunological tolerance to xenogeneic islets remains a challenge. METHODS: The current study used a pig-to-mouse discordant xenogeneic islet tran ... Full text Link to item Cite

A Novel Method for Anti-HLA Antibody Detection Using Personalized Peptide Arrays.

Journal Article Transplant Direct · November 2016 BACKGROUND: HLA mismatches are the primary cause of alloantibody-mediated rejection (AMR) in organ transplantation. To delineate antigenic and immunogenic potentials among individual HLA mismatches, information regarding antibody specificity at the epitope ... Full text Link to item Cite

National Institutes of Health-Sponsored Clinical Islet Transplantation Consortium Phase 3 Trial: Manufacture of a Complex Cellular Product at Eight Processing Facilities.

Journal Article Diabetes · November 2016 Featured Publication Eight manufacturing facilities participating in the National Institutes of Health-sponsored Clinical Islet Transplantation (CIT) Consortium jointly developed and implemented a harmonized process for the manufacture of allogeneic purified human pancreatic i ... Full text Link to item Cite

Mold-casted non-degradable, islet macro-encapsulating hydrogel devices for restoration of normoglycemia in diabetic mice.

Journal Article Biotechnol Bioeng · November 2016 Featured Publication Islet transplantation is a potential cure for diabetic patients, however this procedure is not widely adopted due to the high rate of graft failure. Islet encapsulation within hydrogels is employed to provide a three-dimensional microenvironment conducive ... Full text Link to item Cite

Immune Tolerance for Autoimmune Disease and Cell Transplantation.

Journal Article Annu Rev Biomed Eng · July 11, 2016 Featured Publication The undesired destruction of healthy cells, either endogenous or transplanted, by the immune system results in the loss of tissue function or limits strategies to restore tissue function. Current therapies typically involve nonspecific immunosuppression th ... Full text Link to item Cite

Phase 3 Trial of Transplantation of Human Islets in Type 1 Diabetes Complicated by Severe Hypoglycemia.

Journal Article Diabetes Care · July 2016 Featured Publication OBJECTIVE: Impaired awareness of hypoglycemia (IAH) and severe hypoglycemic events (SHEs) cause substantial morbidity and mortality in patients with type 1 diabetes (T1D). Current therapies are effective in preventing SHEs in 50-80% of patients with IAH an ... Full text Link to item Cite

Recipient Myd88 Deficiency Promotes Spontaneous Resolution of Kidney Allograft Rejection.

Journal Article J Am Soc Nephrol · November 2015 The myeloid differentiation protein 88 (MyD88) adapter protein is an important mediator of kidney allograft rejection, yet the precise role of MyD88 signaling in directing the host immune response toward the development of kidney allograft rejection remain ... Full text Link to item Cite

THERAPY OF ENDOCRINE DISEASE: Islet transplantation for type 1 diabetes: so close and yet so far away.

Journal Article Eur J Endocrinol · November 2015 Featured Publication Over the past decades, tremendous efforts have been made to establish pancreatic islet transplantation as a standard therapy for type 1 diabetes. Recent advances in islet transplantation have resulted in steady improvements in the 5-year insulin independen ... Full text Link to item Cite

Cellular and molecular targeting for nanotherapeutics in transplantation tolerance.

Journal Article Clin Immunol · September 2015 Featured Publication The induction of donor-specific tolerance to transplanted cells and organs, while preserving immune function as a whole, remains a highly sought after and elusive strategy for overcoming transplant rejection. Tolerance necessitates modulating a diverse arr ... Full text Link to item Cite

Tempering allorecognition to induce transplant tolerance with chemically modified apoptotic donor cells.

Journal Article Am J Transplant · June 2015 The development of organ transplantation as a therapy for end-stage organ failure is among the most significant achievements of 20th century medicine, but chronic rejection remains a barrier to achieving long-term success. Current therapeutic regimens cons ... Full text Link to item Cite

Literature Watch Implications for transplantation

Journal Article American Journal of Transplantation · February 1, 2015 This month, ‘Literature Watch’ examines data suggesting that the circadian clock may influence the graft-immune interface via its modulation of both innate and adaptive responses encountered during transplantation. ... Full text Cite

Preemptive Tolerogenic Delivery of Donor Antigens for Permanent Allogeneic Islet Graft Protection.

Journal Article Cell Transplant · 2015 Featured Publication We have previously developed a robust regimen for tolerance induction in murine models of islet cell transplantation using pre- and posttransplant infusions of donor splenocytes (SPs) treated with a chemical cross-linker ethylcarbodiimide (ECDI). However, ... Full text Link to item Cite

Nanoparticle delivery of donor antigens for transplant tolerance in allogeneic islet transplantation.

Journal Article Biomaterials · October 2014 Human islet cell transplantation is a promising treatment for type 1 diabetes; however, long-term donor-specific tolerance to islet allografts remains a clinically unmet goal. We have previously shown that recipient infusions of apoptotic donor splenocytes ... Full text Link to item Cite

Enhancing human islet transplantation by localized release of trophic factors from PLG scaffolds.

Journal Article Am J Transplant · July 2014 Featured Publication Islet transplantation represents a potential cure for type 1 diabetes, yet the clinical approach of intrahepatic delivery is limited by the microenvironment. Microporous scaffolds enable extrahepatic transplantation, and the microenvironment can be designe ... Full text Link to item Cite

Preemptive donor apoptotic cell infusions induce IFN-γ-producing myeloid-derived suppressor cells for cardiac allograft protection.

Journal Article J Immunol · June 15, 2014 Featured Publication We have previously shown that preemptive infusion of apoptotic donor splenocytes treated with the chemical cross-linker ethylcarbodiimide (ECDI-SPs) induces long-term allograft survival in full MHC-mismatched models of allogeneic islet and cardiac transpla ... Full text Link to item Cite

IL-15 expanded CD8+CD122+ cells: when do they suppress?

Journal Article Am J Transplant · January 2014 Featured Publication Full text Link to item Cite

Transient B-cell depletion combined with apoptotic donor splenocytes induces xeno-specific T- and B-cell tolerance to islet xenografts.

Journal Article Diabetes · September 2013 Peritransplant infusion of apoptotic donor splenocytes cross-linked with ethylene carbodiimide (ECDI-SPs) has been demonstrated to effectively induce allogeneic donor-specific tolerance. The objective of the current study is to determine the effectiveness ... Full text Link to item Cite

PLG scaffold delivered antigen-specific regulatory T cells induce systemic tolerance in autoimmune diabetes.

Journal Article Tissue Eng Part A · June 2013 Islet transplantation is a promising treatment for human type 1 diabetes mellitus. Transplantation requires systemic immunosuppression, which has numerous deleterious side effects. Islet antigen-specific regulatory T cells (Tregs) have been shown to protec ... Full text Link to item Cite

Microparticles bearing encephalitogenic peptides induce T-cell tolerance and ameliorate experimental autoimmune encephalomyelitis.

Journal Article Nat Biotechnol · December 2012 Aberrant T-cell activation underlies many autoimmune disorders, yet most attempts to induce T-cell tolerance have failed. Building on previous strategies for tolerance induction that exploited natural mechanisms for clearing apoptotic debris, we show that ... Full text Link to item Cite

Pathogenesis of NOD diabetes is initiated by reactivity to the insulin B chain 9-23 epitope and involves functional epitope spreading.

Journal Article J Autoimmun · December 2012 Type 1 diabetes (T1D) is mediated by destruction of pancreatic β-cells by CD4 and CD8 T cells specific for epitopes on numerous diabetogenic autoantigens resulting in loss of glucose homeostasis. Employing antigen-specific tolerance induced by i.v. adminis ... Full text Link to item Cite

Intragraft CD11b(+) IDO(+) cells mediate cardiac allograft tolerance by ECDI-fixed donor splenocyte infusions.

Journal Article Am J Transplant · November 2012 We have previously shown that pre- and post-transplant infusions of donor splenocytes treated with 1-ethyl-3-(3'-dimethylaminopropyl)-carbodiimide (ECDI-SPs) provide permanent donor-specific protection of islet allografts. The efficacy of donor ECDI-SPs in ... Full text Link to item Cite

Donor-specific CD8+ Foxp3+ T cells protect skin allografts and facilitate induction of conventional CD4+ Foxp3+ regulatory T cells.

Journal Article Am J Transplant · September 2012 CD4(+) regulatory T cells play a critical role in tolerance induction in transplantation. CD8(+) suppressor T cells have also been shown to control alloimmune responses in preclinical and clinical models. However, the exact nature of the CD8(+) suppressor ... Full text Link to item Cite

Ethylenecarbodiimide-fixed donor splenocyte infusions differentially target direct and indirect pathways of allorecognition for induction of transplant tolerance.

Journal Article J Immunol · July 15, 2012 Strategic exposure to donor Ags prior to transplantation can be an effective way for inducting donor-specific tolerance in allogeneic recipients. We have recently shown that pretransplant infusion of donor splenocytes treated with the chemical cross-linker ... Full text Link to item Cite

Improvement in outcomes of clinical islet transplantation: 1999-2010.

Journal Article Diabetes Care · July 2012 OBJECTIVE: To describe trends of primary efficacy and safety outcomes of islet transplantation in type 1 diabetes recipients with severe hypoglycemia from the Collaborative Islet Transplant Registry (CITR) from 1999 to 2010. RESEARCH DESIGN AND METHODS: A ... Full text Link to item Cite

Advancing islet transplantation: from engraftment to the immune response.

Journal Article Diabetologia · October 2011 The promise and progress of islet transplantation for treating type 1 diabetes has been challenged by obstacles to patient accessibility and long-term graft function that may be overcome by integrating emerging technologies in biomaterials, drug delivery a ... Full text Link to item Cite

Tolerance induced by apoptotic antigen-coupled leukocytes is induced by PD-L1+ and IL-10-producing splenic macrophages and maintained by T regulatory cells.

Journal Article J Immunol · September 1, 2011 Ag-specific tolerance is a highly desired therapy for immune-mediated diseases. Intravenous infusion of protein/peptide Ags linked to syngeneic splenic leukocytes with ethylene carbodiimide (Ag-coupled splenocytes [Ag-SP]) has been demonstrated to be a hig ... Full text Link to item Cite

Permanent protection of PLG scaffold transplanted allogeneic islet grafts in diabetic mice treated with ECDI-fixed donor splenocyte infusions.

Journal Article Biomaterials · July 2011 Allogeneic islet cell transplantation is a promising treatment for human type 1 diabetes. Currently, human islets are transplanted via intra-portal infusions. While successful, it leads to significant early islet attrition from instant blood-mediated infla ... Full text Link to item Cite

Prevention and treatment of diabetes with resveratrol in a non-obese mouse model of type 1 diabetes.

Journal Article Diabetologia · May 2011 AIMS/HYPOTHESIS: We recently found that activation of the type III histone deacetylase sirtuin 1 suppresses T cell immune responses. Here we sought to determine the therapeutic potential of the sirtuin 1 activator resveratrol in the treatment of diabetes i ... Full text Link to item Cite

Lymphocyte activation markers may predict the presence of donor specific alloreactivity in pediatric living related liver transplant recipients.

Journal Article Hum Immunol · May 2011 This is an observational study with the primary objective to measure donor-specific immune responses by pediatric liver transplant (LT) recipients, using cell surface expression of lymphocyte activation markers and cytokine secretion in mixed lymphocyte re ... Full text Link to item Cite

Common gamma chain cytokines promote rapid in vitro expansion of allo-specific human CD8+ suppressor T cells.

Journal Article PLoS One · 2011 Human CD8(+) regulatory T cells, particularly the CD8(+)CD28(-) T suppressor cells, have emerged as an important modulator of alloimmunity. Understanding the conditions under which these cells are induced and/or expanded would greatly facilitate their appl ... Full text Link to item Cite

Requirement of cognate CD4+ T-cell recognition for the regulation of allospecific CTL by human CD4+ CD127- CD25+ FOXP3+ cells generated in MLR.

Journal Article PLoS One · 2011 Although immunoregulation of alloreactive human CTLs has been described, the direct influence of CD4(+) Tregs on CD8(+) cytotoxicity and the interactive mechanisms have not been well clarified. Therefore, human CD4(+)CD127(-)CD25(+)FOXP3(+) Tregs were gene ... Full text Link to item Cite

Ethylenecarbodiimide-treated splenocytes carrying male CD4 epitopes confer histocompatibility Y chromosome antigen transplant protection by inhibiting CD154 upregulation.

Journal Article J Immunol · September 15, 2010 In humans and certain strains of laboratory mice, male tissue is recognized as nonself and destroyed by the female immune system via recognition of histocompatibility Y chromosome Ag (Hya). Male tissue destruction is thought to be accomplished by CTLs in a ... Full text Link to item Cite

Rapamycin-conditioned donor dendritic cells differentiate CD4CD25Foxp3 T cells in vitro with TGF-beta1 for islet transplantation.

Journal Article Am J Transplant · August 2010 Dendritic cells (DCs) conditioned with the mammalian target of rapamycin (mTOR) inhibitor rapamycin have been previously shown to expand naturally existing regulatory T cells (nTregs). This work addresses whether rapamycin-conditioned donor DCs could effec ... Full text Link to item Cite

TGF-beta-induced myelin peptide-specific regulatory T cells mediate antigen-specific suppression of induction of experimental autoimmune encephalomyelitis.

Journal Article J Immunol · June 15, 2010 The low number of natural regulatory T cells (nTregs) in the circulation specific for a particular Ag and concerns about the bystander suppressive capacity of expanded nTregs presents a major clinical challenge for nTreg-based therapeutic treatment of auto ... Full text Link to item Cite

Immunotherapy of type 1 diabetes: where are we and where should we be going?

Journal Article Immunity · April 23, 2010 Type 1 diabetes (T1D) is a chronic autoimmune disorder characterized by destruction of insulin-producing pancreatic beta cells. Many broad-based immunosuppressive and antigen-specific immunoregulatory therapies have been and are currently being evaluated f ... Full text Link to item Cite

A decade of minimally invasive donation: experience with more than 1200 laparoscopic donor nephrectomies at a single institution.

Journal Article Clin Transplant · 2010 BACKGROUND: The past decade has seen laparoscopic donor nephrectomy (LDN) transform into a standard of care procedure. Furthermore, LDN has evolved with the introduction of new technologies aimed at increasing efficiency and safety. There are few large, si ... Full text Link to item Cite

Perception versus reality?: Virtual crossmatch--how to overcome some of the technical and logistic limitations.

Journal Article Am J Transplant · August 2009 The goal of this work was to evaluate concordance between (a) actual flow cytometric crossmatch (FCXM) that is performed by the OPO laboratory servicing our transplant center and (b) virtual XM (vXM) prediction based on antibody identification by solid-pha ... Full text Link to item Cite

Prevention of allograft rejection by amplification of Foxp3(+)CD4(+)CD25(+) regulatory T cells.

Journal Article Transl Res · February 2009 CD4(+)CD25(+) T cells were identified originally as potent suppressors of autoimmunity and were later termed "natural regulatory T cells" or nTreg cells. Subsequently, a transcription factor called forkhead box protein 3 (Foxp3) was identified to be a crit ... Full text Link to item Cite

Impairing oral tolerance promotes allergy and anaphylaxis: a new murine food allergy model.

Journal Article J Allergy Clin Immunol · January 2009 BACKGROUND: Food allergy is a disorder in which antigenic food proteins elicit immune responses. Animal models of food allergy have several limitations that influence their utility, including failure to recapitulate several key immunologic hallmarks. Conse ... Full text Link to item Cite

Intrinsic and induced regulation of the age-associated onset of spontaneous experimental autoimmune encephalomyelitis.

Journal Article J Immunol · October 1, 2008 Multiple sclerosis is characterized by perivascular CNS infiltration of myelin-specific CD4(+) T cells and activated mononuclear cells. TCR transgenic mice on the SJL background specific for proteolipid protein (PLP)(139-151) develop a high incidence of sp ... Full text Link to item Cite

ECDI-fixed allogeneic splenocytes induce donor-specific tolerance for long-term survival of islet transplants via two distinct mechanisms.

Journal Article Proc Natl Acad Sci U S A · September 23, 2008 A major challenge for human allogeneic islet transplantation is the development of effective methods to induce donor-specific tolerance to obviate the need for life-long immunosuppression that is toxic to the insulin-producing beta cells and detrimental to ... Full text Link to item Cite

Cutting edge: TGF-beta-induced expression of Foxp3 in T cells is mediated through inactivation of ERK.

Journal Article J Immunol · March 1, 2008 The peripheral induction of T regulatory cells can be accomplished by TGF-beta through an epigenetic regulation leading to the expression of Foxp3. However, the exact mechanism of such a TGF-beta-mediated action remains unclear. In the current study, we fo ... Full text Link to item Cite

Hyperexpression of Foxp3 and IDO during acute rejection of islet allografts.

Journal Article Transplantation · June 27, 2007 BACKGROUND: We investigated the hypothesis that Foxp3+ cells are an integral component of antiallograft immunity but are dominated by pathogenic effectors. METHODS: Wild-type H-2b C57BL/6 (B6) mice or B6 mice with a targeted disruption of c-Rel gene (c-Rel ... Full text Link to item Cite

Dendritic cells with TGF-beta1 differentiate naive CD4+CD25- T cells into islet-protective Foxp3+ regulatory T cells.

Journal Article Proc Natl Acad Sci U S A · February 20, 2007 CD4(+)CD25(+)Foxp3(+) regulatory T cells (T regs) are important for preventing autoimmune diabetes and are either thymic-derived (natural) or differentiated in the periphery outside the thymus (induced). Here we show that beta-cell peptide-pulsed dendritic ... Full text Link to item Cite

Dendritic cell-expanded, islet-specific CD4+ CD25+ CD62L+ regulatory T cells restore normoglycemia in diabetic NOD mice.

Journal Article J Exp Med · January 22, 2007 Most treatments that prevent autoimmune diabetes in nonobese diabetic (NOD) mice require intervention at early pathogenic stages, when insulitis is first developing. We tested whether dendritic cell (DC)-expanded, islet antigen-specific CD4+ CD25+ suppress ... Full text Link to item Cite

Opportunities for performance improvement in relation to medication administration during pediatric stabilization.

Journal Article Qual Saf Health Care · June 2006 OBJECTIVES: To identify and characterize areas for improvement in the clinical performance of nurses in relation to medication administration. METHOD: Nurses participated in a simulated pediatric stabilization event which was videotaped. Their clinical per ... Full text Link to item Cite

Development of donor-specific and non-donor-specific HLA-DP antibodies post-transplant: the role of epitope sharing and epitope matching.

Journal Article Clin Transpl · 2006 In conclusion, this case provided a unique illustration of de novo production of DSA following transplant from an HLA-A, -B, and -DR matched donor (eliminating the masking effect of these potential mismatches). The antibody generated could be tracked down ... Link to item Cite

Systemic transforming growth factor-beta1 gene therapy induces Foxp3+ regulatory cells, restores self-tolerance, and facilitates regeneration of beta cell function in overtly diabetic nonobese diabetic mice.

Journal Article Transplantation · May 15, 2005 BACKGROUND: Type 1 diabetes results from auto-aggressive T-cell-mediated destruction of beta cells of the pancreas. Recent data suggest that restoration of self-tolerance may facilitate islet-cell regeneration/recovery. In view of the immunoregulatory acti ... Full text Link to item Cite

Steroidogenic factor 1: an essential mediator of endocrine development.

Journal Article Recent Prog Horm Res · 2002 The orphan nuclear receptor steroidogenic factor 1 (SF-1, also called Ad4BP and officially designated NR5A1) has emerged as an essential regulator of endocrine development and function. Initially identified as a tissue-specific transcriptional regulator of ... Full text Link to item Cite

Hepatitis B virus (HBV) reactivation after cytotoxic or immunosuppressive therapy--pathogenesis and management.

Journal Article Rev Med Virol · 2001 In an endemic area for chronic hepatitis B infection, reactivation of this virus is a serious cause of morbidity and mortality in patients undergoing cytotoxic or immunosuppressive therapy. Careful prospective serological testing has shown that hepatitis B ... Full text Link to item Cite

Steroidogenic factor 1 (SF-1) is essential for ovarian development and function.

Journal Article Mol Cell Endocrinol · May 25, 2000 The orphan nuclear receptor steroidogenic factor 1 (SF-1) was identified originally as a key regulator of the tissue-specific expression of the cytochrome P450 steroid hydroxylases. Hints at considerably broader roles for SF-1 came from analyses of its exp ... Full text Link to item Cite

Steroidogenic factor 1 (SF-1) is essential for endocrine development and function.

Conference J Steroid Biochem Mol Biol · 1999 Steroidogenic factor 1 (SF-1), an orphan nuclear receptor, initially was isolated as a key regulator of the tissue-specific expression of the cytochrome P450 steroid hydroxylases. Thereafter, analyses of sites of SF-1 expression during mouse embryological ... Full text Link to item Cite

Steroidogenic factor 1 plays multiple roles in endocrine development and function.

Journal Article Recent Prog Horm Res · 1997 The nuclear hormone receptor family comprises a group of structurally related transcriptional regulators that mediate the actions of diverse ligands, including steroid hormones, thyroid hormone, vitamin D, and retinoids. The nuclear receptor family also co ... Link to item Cite

The roles of steroidogenic factor-1 in reproductive function.

Conference Steroids · April 1996 The cytochrome P450 steroid hydroxylases are expressed in a tissue-specific and developmentally regulated manner, and the orphan nuclear receptor steroidogenic factor 1 (SF-1) participates in both aspects of regulated expression. SF-1 is expressed in mouse ... Full text Link to item Cite

The cell-specific nuclear receptor steroidogenic factor 1 plays multiple roles in reproductive function.

Journal Article Philos Trans R Soc Lond B Biol Sci · November 29, 1995 The cytochrome P450 steroid hydroxylases exhibit tissue-specific and developmentally regulated gene expression. Recent studies showed that the orphan nuclear receptor steroidogenic factor 1 (SF-1) plays a key role in their gene regulation. In mouse embryos ... Full text Link to item Cite

Steroidogenic factor 1 is the essential transcript of the mouse Ftz-F1 gene.

Journal Article Mol Endocrinol · September 1995 Targeted disruption of the mouse Ftz-F1 gene, which encodes the orphan nuclear receptors steroidogenic factor 1 (SF-1) and embryonal long terminal repeat-binding protein (ELP), established that this gene is essential for development of the primary steroido ... Full text Link to item Cite

The nuclear receptor steroidogenic factor 1 is essential for the formation of the ventromedial hypothalamic nucleus.

Journal Article Mol Endocrinol · April 1995 The nuclear receptor steroidogenic factor 1 (SF-1) regulates the biosynthesis of the two essential mediators of male sexual differentiation, androgens and Müllerian-inhibiting substance, and is required for adrenal and gonadal development and gonadotropin ... Full text Link to item Cite

A cell-specific nuclear receptor regulates the steroid hydroxylases.

Journal Article Steroids · January 1995 Recent studies of the gene regulation of the cytochrome P450 steroid hydroxylases have established a key role for an orphan nuclear receptor, designated steroidogenic factor 1 (SF-1). SF-1 binds to shared promoter elements upstream of the steroid hydroxyla ... Full text Link to item Cite

A cell-specific nuclear receptor plays essential roles in adrenal and gonadal development.

Journal Article Endocr Res · 1995 Recent analyses of the cytochrome P450 steroid hydroxylases have established a key role for an orphan nuclear receptor, designated steroidogenic factor 1 (SF-1), in their coordinate, cell-selective expression. SF-1 was proposed to regulate the steroid hydr ... Full text Link to item Cite

The nuclear receptor steroidogenic factor 1 acts at multiple levels of the reproductive axis.

Journal Article Genes Dev · October 1, 1994 Steroidogenic factor 1 (SF-1), an orphan nuclear receptor, regulates the enzymes that produce sex steroids, and disruption of the Ftz-F1 gene encoding SF-1 precludes adrenal and gonadal development. We now study the role of SF-1 at other levels of the hypo ... Full text Link to item Cite

A cell-specific nuclear receptor is essential for adrenal and gonadal development and sexual differentiation.

Journal Article Cell · May 20, 1994 Studies in adrenocortical cells have implicated the orphan nuclear receptor SF-1 in the gene regulation of the steroid hydroxylases. We used targeted disruption of the Ftz-F1 gene, which encodes SF-1, to examine its role in intact mice. Despite normal surv ... Full text Link to item Cite

Characterization of the mouse FTZ-F1 gene, which encodes a key regulator of steroid hydroxylase gene expression.

Journal Article Mol Endocrinol · July 1993 The cytochrome P450 steroid hydroxylases are coordinately regulated by steroidogenic factor 1 (SF-1), a protein expressed selectively in steroidogenic cells. Based on its expression in steroidogenic tissues and DNA-binding specificity, we isolated a putati ... Full text Link to item Cite