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Mari L. Shinohara

Professor of Integrative Immunobiology
Integrative Immunobiology
Box 3010 DUMC, 338 Jones Building, Durham, NC 27710
338 Jones Building, 207 Research Dr., Box 3010 DUMC, Dept of Immunology, Durham, NC 27710

Selected Publications


Subventricular zone stem cell niche injury is associated with intestinal perforation in preterm infants and predicts future motor impairment.

Journal Article Cell Stem Cell · April 4, 2024 Brain injury is highly associated with preterm birth. Complications of prematurity, including spontaneous or necrotizing enterocolitis (NEC)-associated intestinal perforations, are linked to lifelong neurologic impairment, yet the mechanisms are poorly und ... Full text Link to item Cite

Integrin α3 promotes TH17 cell polarization and extravasation during autoimmune neuroinflammation.

Journal Article Sci Immunol · October 20, 2023 Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) caused by CNS-infiltrating leukocytes, including TH17 cells that are critical mediators of disease pathogenesis. Although targeting leukocyte trafficking is effective in t ... Full text Link to item Cite

A binary module for microbiota-mediated regulation of γδ17 cells, hallmarked by microbiota-driven expression of programmed cell death protein 1.

Journal Article Cell Rep · August 29, 2023 Little is known about how microbiota regulate innate-like γδ T cells or how these restrict their effector functions within mucosal barriers, where microbiota provide chronic stimulation. Here, we show that microbiota-mediated regulation of γδ17 cells is bi ... Full text Link to item Cite

20-αHydroxycholesterol, an oxysterol in human breast milk, reverses mouse neonatal white matter injury through Gli-dependent oligodendrogenesis.

Journal Article Cell Stem Cell · August 3, 2023 White matter injuries (WMIs) are the leading cause of neurologic impairment in infants born premature. There are no treatment options available. The most common forms of WMIs in infants occur prior to the onset of normal myelination, making its pathophysio ... Full text Link to item Cite

Osteopontin (OPN)/SPP1: from its biochemistry to biological functions in the innate immune system and the central nervous system (CNS).

Journal Article International immunology · April 2023 Osteopontin (OPN) is a multifunctional protein, initially identified in osteosarcoma cells with its role of mediating osteoblast adhesion. Later studies revealed that OPN is associated with many inflammatory conditions caused by infections, allergic respon ... Full text Cite

Microglia C-lectin/selectin' neurons to eat.

Journal Article Immunity · February 14, 2023 Featured Publication β-glucosylceramide (β-GlcCer) accumulates in Gaucher disease, but how β-GlcCer, a Mincle ligand, causes characteristic neuroinflammation and neuronopathy is poorly understood. In this issue of Immunity, Shimizu et al. reveal that Mincle-dependent activatio ... Full text Link to item Cite

Dectin-1 signaling in neutrophils up-regulates PD-L1 and triggers ROS-mediated suppression of CD4+ T cells.

Journal Article J Leukoc Biol · December 2022 Dectin-1 is known to drive proinflammatory cytokine production by macrophages and dendritic cells which promotes Th17 CD4+ T cell responses in the setting of fungal infection. However, the role of Dectin-1 signaling in neutrophils and its impact on CD4+ T ... Full text Link to item Cite

Loss of Zfp335 triggers cGAS/STING-dependent apoptosis of post-β selection thymocytes.

Journal Article Nat Commun · October 6, 2022 Production of a functional peripheral T cell compartment typically involves massive expansion of the bone marrow progenitors that seed the thymus. There are two main phases of expansion during T cell development, following T lineage commitment of double-ne ... Full text Link to item Cite

Host immune responses in the central nervous system during fungal infections.

Journal Article Immunol Rev · October 2022 Featured Publication Fungal infections in the central nervous system (CNS) cause high morbidity and mortality. The frequency of CNS mycosis has increased over the last two decades as more individuals go through immunocompromised conditions for various reasons. Nevertheless, op ... Full text Link to item Cite

Infection and inflammation: New perspectives on Alzheimer's disease.

Journal Article Brain Behav Immun Health · July 2022 Neuroinflammation has been recognized as a component of Alzheimer's Disease (AD) pathology since the original descriptions by Alois Alzheimer and a role for infections in AD pathogenesis has long been hypothesized. More recently, this hypothesis has gained ... Full text Link to item Cite

Loss of Zfp335 triggers cGAS/STING-dependent apoptosis of post-β selection pre-T cells

Conference The Journal of Immunology · May 1, 2022 AbstractProduction of a diverse peripheral T cell compartment requires massive expansion of the bone marrow progenitors that seed the thymus. There are two main phases of expansion during T cell development, ... Full text Cite

The AIM2 inflammasome is activated in astrocytes during the late phase of EAE.

Journal Article JCI Insight · April 22, 2022 Featured Publication Inflammasomes are a class of innate immune signaling platforms that activate in response to an array of cellular damage and pathogens. Inflammasomes promote inflammation under many circumstances to enhance immunity against pathogens and inflammatory respon ... Full text Link to item Cite

Annexin-A1 Tripeptide Attenuates Surgery-Induced Neuroinflammation and Memory Deficits Through Regulation the NLRP3 Inflammasome.

Journal Article Front Immunol · 2022 Neuroinflammation is a growing hallmark of perioperative neurocognitive disorders (PNDs), including delirium and longer-lasting cognitive deficits. We have developed a clinically relevant orthopedic mouse model to study the impact of a common surgical proc ... Full text Link to item Cite

Secreted osteopontin from CD4+ T cells limits acute graft-versus-host disease.

Journal Article Cell Rep · December 28, 2021 Featured Publication Osteopontin (OPN) has been considered a potential biomarker of graft-versus-host disease (GVHD). However, the function of OPN in GVHD is still elusive. Using a mouse model of acute GVHD (aGVHD), we report that OPN generated by CD4+ T cells is sufficient to ... Full text Link to item Cite

AIM2 inflammasome activation in astrocytes occurs during the late phase of EAE

Journal Article · October 5, 2021 Featured Publication ABSTRACTInflammasomes are a class of innate immune signaling platforms that activate in response to an array of cellular damage and pathogens. Inflammasomes promote inflammation under many circumstances to enhance immunity ... Full text Cite

Emerging roles of Dectin-1 in noninfectious settings and in the CNS.

Journal Article Trends Immunol · October 2021 Featured Publication Dectin-1 is a C-type lectin receptor (CLR) expressed on the surface of various mammalian myeloid cells. Dectin-1 recognizes β-glucans and elicits antifungal proinflammatory immune responses. Recent studies have begun to examine the biology of Dectin-1 in p ... Full text Link to item Cite

Targeting Inflammasomes to Treat Neurological Diseases.

Journal Article Ann Neurol · August 2021 Inflammasomes are multimeric protein complexes that can sense a plethora of microbe- and damage-associated molecular signals. They play important roles in innate immunity and are key regulators of inflammation in health and disease. Inflammasome-mediated p ... Full text Link to item Cite

Subventricular zone stem cell niche injury is associated with intestinal perforation in preterm infants and predicts future motor impairment.

Journal Article Cell Stem Cell · April 4, 2024 Brain injury is highly associated with preterm birth. Complications of prematurity, including spontaneous or necrotizing enterocolitis (NEC)-associated intestinal perforations, are linked to lifelong neurologic impairment, yet the mechanisms are poorly und ... Full text Link to item Cite

Integrin α3 promotes TH17 cell polarization and extravasation during autoimmune neuroinflammation.

Journal Article Sci Immunol · October 20, 2023 Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) caused by CNS-infiltrating leukocytes, including TH17 cells that are critical mediators of disease pathogenesis. Although targeting leukocyte trafficking is effective in t ... Full text Link to item Cite

A binary module for microbiota-mediated regulation of γδ17 cells, hallmarked by microbiota-driven expression of programmed cell death protein 1.

Journal Article Cell Rep · August 29, 2023 Little is known about how microbiota regulate innate-like γδ T cells or how these restrict their effector functions within mucosal barriers, where microbiota provide chronic stimulation. Here, we show that microbiota-mediated regulation of γδ17 cells is bi ... Full text Link to item Cite

20-αHydroxycholesterol, an oxysterol in human breast milk, reverses mouse neonatal white matter injury through Gli-dependent oligodendrogenesis.

Journal Article Cell Stem Cell · August 3, 2023 White matter injuries (WMIs) are the leading cause of neurologic impairment in infants born premature. There are no treatment options available. The most common forms of WMIs in infants occur prior to the onset of normal myelination, making its pathophysio ... Full text Link to item Cite

Osteopontin (OPN)/SPP1: from its biochemistry to biological functions in the innate immune system and the central nervous system (CNS).

Journal Article International immunology · April 2023 Osteopontin (OPN) is a multifunctional protein, initially identified in osteosarcoma cells with its role of mediating osteoblast adhesion. Later studies revealed that OPN is associated with many inflammatory conditions caused by infections, allergic respon ... Full text Cite

Microglia C-lectin/selectin' neurons to eat.

Journal Article Immunity · February 14, 2023 Featured Publication β-glucosylceramide (β-GlcCer) accumulates in Gaucher disease, but how β-GlcCer, a Mincle ligand, causes characteristic neuroinflammation and neuronopathy is poorly understood. In this issue of Immunity, Shimizu et al. reveal that Mincle-dependent activatio ... Full text Link to item Cite

Dectin-1 signaling in neutrophils up-regulates PD-L1 and triggers ROS-mediated suppression of CD4+ T cells.

Journal Article J Leukoc Biol · December 2022 Dectin-1 is known to drive proinflammatory cytokine production by macrophages and dendritic cells which promotes Th17 CD4+ T cell responses in the setting of fungal infection. However, the role of Dectin-1 signaling in neutrophils and its impact on CD4+ T ... Full text Link to item Cite

Loss of Zfp335 triggers cGAS/STING-dependent apoptosis of post-β selection thymocytes.

Journal Article Nat Commun · October 6, 2022 Production of a functional peripheral T cell compartment typically involves massive expansion of the bone marrow progenitors that seed the thymus. There are two main phases of expansion during T cell development, following T lineage commitment of double-ne ... Full text Link to item Cite

Host immune responses in the central nervous system during fungal infections.

Journal Article Immunol Rev · October 2022 Featured Publication Fungal infections in the central nervous system (CNS) cause high morbidity and mortality. The frequency of CNS mycosis has increased over the last two decades as more individuals go through immunocompromised conditions for various reasons. Nevertheless, op ... Full text Link to item Cite

Infection and inflammation: New perspectives on Alzheimer's disease.

Journal Article Brain Behav Immun Health · July 2022 Neuroinflammation has been recognized as a component of Alzheimer's Disease (AD) pathology since the original descriptions by Alois Alzheimer and a role for infections in AD pathogenesis has long been hypothesized. More recently, this hypothesis has gained ... Full text Link to item Cite

Loss of Zfp335 triggers cGAS/STING-dependent apoptosis of post-β selection pre-T cells

Conference The Journal of Immunology · May 1, 2022 AbstractProduction of a diverse peripheral T cell compartment requires massive expansion of the bone marrow progenitors that seed the thymus. There are two main phases of expansion during T cell development, ... Full text Cite

The AIM2 inflammasome is activated in astrocytes during the late phase of EAE.

Journal Article JCI Insight · April 22, 2022 Featured Publication Inflammasomes are a class of innate immune signaling platforms that activate in response to an array of cellular damage and pathogens. Inflammasomes promote inflammation under many circumstances to enhance immunity against pathogens and inflammatory respon ... Full text Link to item Cite

Annexin-A1 Tripeptide Attenuates Surgery-Induced Neuroinflammation and Memory Deficits Through Regulation the NLRP3 Inflammasome.

Journal Article Front Immunol · 2022 Neuroinflammation is a growing hallmark of perioperative neurocognitive disorders (PNDs), including delirium and longer-lasting cognitive deficits. We have developed a clinically relevant orthopedic mouse model to study the impact of a common surgical proc ... Full text Link to item Cite

Secreted osteopontin from CD4+ T cells limits acute graft-versus-host disease.

Journal Article Cell Rep · December 28, 2021 Featured Publication Osteopontin (OPN) has been considered a potential biomarker of graft-versus-host disease (GVHD). However, the function of OPN in GVHD is still elusive. Using a mouse model of acute GVHD (aGVHD), we report that OPN generated by CD4+ T cells is sufficient to ... Full text Link to item Cite

AIM2 inflammasome activation in astrocytes occurs during the late phase of EAE

Journal Article · October 5, 2021 Featured Publication ABSTRACTInflammasomes are a class of innate immune signaling platforms that activate in response to an array of cellular damage and pathogens. Inflammasomes promote inflammation under many circumstances to enhance immunity ... Full text Cite

Emerging roles of Dectin-1 in noninfectious settings and in the CNS.

Journal Article Trends Immunol · October 2021 Featured Publication Dectin-1 is a C-type lectin receptor (CLR) expressed on the surface of various mammalian myeloid cells. Dectin-1 recognizes β-glucans and elicits antifungal proinflammatory immune responses. Recent studies have begun to examine the biology of Dectin-1 in p ... Full text Link to item Cite

Targeting Inflammasomes to Treat Neurological Diseases.

Journal Article Ann Neurol · August 2021 Inflammasomes are multimeric protein complexes that can sense a plethora of microbe- and damage-associated molecular signals. They play important roles in innate immunity and are key regulators of inflammation in health and disease. Inflammasome-mediated p ... Full text Link to item Cite

Dectin-1 limits autoimmune neuroinflammation and promotes myeloid cell-astrocyte crosstalk via Card9-independent expression of Oncostatin M.

Journal Article Immunity · March 9, 2021 Featured Publication Pathologic roles of innate immunity in neurologic disorders are well described, but their beneficial aspects are less understood. Dectin-1, a C-type lectin receptor (CLR), is largely known to induce inflammation. Here, we report that Dectin-1 limited exper ... Full text Link to item Cite

Single-Cell Transcriptional Heterogeneity of Neutrophils During Acute Pulmonary Cryptococcus neoformans Infection.

Journal Article Front Immunol · 2021 Featured Publication Neutrophils are critical as the first-line defense against fungal pathogens. Yet, previous studies indicate that neutrophil function is complex during Cryptococcus neoformans (Cn) infection. To better understand the role of neutrophils in acute pulmonary c ... Full text Link to item Cite

The Ubiquitin-Modifying Enzyme A20 Terminates C-Type Lectin Receptor Signals and Is a Suppressor of Host Defense against Systemic Fungal Infection.

Journal Article Infect Immun · August 19, 2020 C-type lectin receptors (CLRs) play key roles in antifungal defense. CLR-induced NF-κB is central to CLR functions in immunity, and thus, molecules that control the amplitude of CLR-induced NF-κB could profoundly influence host defense against fungal patho ... Full text Link to item Cite

Functional heterogeneity of alveolar macrophage population based on expression of CXCL2.

Journal Article Sci Immunol · August 7, 2020 Featured Publication Alveolar macrophages (AMs) are the major lung-resident macrophages and have contradictory functions. AMs maintain tolerance and tissue homeostasis, but they also initiate strong inflammatory responses. However, such opposing roles within the AM population ... Full text Link to item Cite

Core N-Glycan Structures Are Critical for the Pathogenicity of Cryptococcus neoformans by Modulating Host Cell Death.

Journal Article mBio · May 12, 2020 Cryptococcus neoformans is a human-pathogenic fungal pathogen that causes life-threatening meningoencephalitis in immunocompromised individuals. To investigate the roles of N-glycan core structure in cryptococcal pathogenicity, we constructed mutant strain ... Full text Link to item Cite

Dectin-1 limits central nervous system autoimmunity through a non-canonical pathway

Conference · May 8, 2020 ABSTRACTPathologic roles for innate immunity in neurologic disorders are well-described, but protective aspects of the immune response are less understood. Dectin-1, a C-type lectin receptor (CLR), is largely known to induc ... Full text Cite

Yolk-sac-derived macrophages progressively expand in the mouse kidney with age.

Journal Article Elife · April 17, 2020 Renal macrophages represent a highly heterogeneous and specialized population of myeloid cells with mixed developmental origins from the yolk-sac and hematopoietic stem cells (HSC). They promote both injury and repair by regulating inflammation, angiogenes ... Full text Link to item Cite

Erythromyeloid progenitors give rise to a population of osteoclasts that contribute to bone homeostasis and repair.

Journal Article Nat Cell Biol · January 2020 Featured Publication Osteoclasts are multinucleated cells of the monocyte/macrophage lineage that degrade bone. Here, we used lineage tracing studies-labelling cells expressing Cx3cr1, Csf1r or Flt3-to identify the precursors of osteoclasts in mice. We identified an erythromye ... Full text Link to item Cite

Th1-Dependent Cryptococcus-Associated Immune Reconstitution Inflammatory Syndrome Model With Brain Damage.

Journal Article Front Immunol · 2020 Featured Publication Cryptococcus-associated immune reconstitution inflammatory syndrome (C-IRIS) is identified upon immune reconstitution in immunocompromised patients, who have previously contracted an infection of Cryptococcus neoformans (Cn). C-IRIS can be lethal but how t ... Full text Link to item Cite

Pattern Recognition Receptors in Multiple Sclerosis and Its Animal Models.

Journal Article Front Immunol · 2019 Pattern recognition receptors (PRRs) coordinate the innate immune response and have a significant role in the development of multiple sclerosis (MS). Accumulating evidence has identified both pathogenic and protective functions of PRR signaling in MS and i ... Full text Link to item Cite

Are Neuropeptide-Reactive T Cells behind Narcolepsy?

Journal Article Immunity · November 20, 2018 Researchers have previously hypothesized autoimmune origins for narcolepsy on the basis of its strong genetic association with an MHC class II allele. In a recent issue of Nature, Latorre et al. (2018) discovered that narcolepsy patients had autoreactive T ... Full text Link to item Cite

Understanding mechanisms underlying the pathology of immune reconstitution inflammatory syndrome (IRIS) by using animal models.

Journal Article Curr Clin Microbiol Rep · September 2018 PURPOSE OF REVIEW: Despite the increasing number of clinical reports on immune reconstitution inflammatory syndrome (IRIS), mechanistic understanding of IRIS is still largely limited. The main focus of this review is to summarize animal studies, which were ... Full text Link to item Cite

Skewing of the population balance of lymphoid and myeloid cells by secreted and intracellular osteopontin.

Journal Article Nat Immunol · September 2017 Featured Publication The balance of myeloid populations and lymphoid populations must be well controlled. Here we found that osteopontin (OPN) skewed this balance during pathogenic conditions such as infection and autoimmunity. Notably, two isoforms of OPN exerted distinct eff ... Full text Open Access Link to item Cite

Inflammasome expression and cytomegalovirus viremia in critically ill patients with sepsis.

Journal Article J Clin Virol · August 2017 BACKGROUND: CMV viremia is a contributor to poor outcomes in critically ill patients with sepsis. OBJECTIVES: To assess the expression levels of genes encoding inflammasome-related proteins in the development of CMV viremia in critically ill patients with ... Full text Link to item Cite

Yes, research matters.

Journal Article PLoS Pathog · August 2017 My father was diagnosed with stomach cancer recently. Luckily, it was still at an early stage, and endoscopic surgery successfully took care of it. My father was fortunate; since people with stomach cancer do not show clear symptoms in the early stages, th ... Full text Link to item Cite

Metabolic Alterations Contribute to Enhanced Inflammatory Cytokine Production in Irgm1-deficient Macrophages.

Journal Article J Biol Chem · March 17, 2017 The immunity-related GTPases (IRGs) are a family of proteins that are induced by interferon (IFN)-γ and play pivotal roles in immune and inflammatory responses. IRGs ostensibly function as dynamin-like proteins that bind to intracellular membranes and prom ... Full text Link to item Cite

Inflammasome activation in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE).

Journal Article Brain Pathol · March 2017 Featured Publication The aptly named inflammasomes are powerful signaling complexes that sense inflammatory signals under a myriad of conditions, including those from infections and endogenous sources. The inflammasomes promote inflammation by maturation and release of the pro ... Full text Link to item Cite

Tissue-Resident Macrophages in Fungal Infections.

Journal Article Front Immunol · 2017 Invasive fungal infections result in high morbidity and mortality. Host organs targeted by fungal pathogens vary depending on the route of infection and fungal species encountered. Cryptococcus neoformans infects the respiratory tract and disseminates thro ... Full text Open Access Link to item Cite

An interferon-β-resistant and NLRP3 inflammasome-independent subtype of EAE with neuronal damage.

Journal Article Nat Neurosci · December 2016 Inflammation induced by innate immunity influences the development of T cell-mediated autoimmunity in multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). We found that strong activation of innate immunity induced Nod-l ... Full text Link to item Cite

Osteopontin has a protective role in prostate tumor development in mice.

Journal Article Eur J Immunol · November 2016 Osteopontin (OPN) is a protein, generally considered to play a pro-tumorigenic role, whereas several reports have demonstrated the anti-tumorigenic function of OPN during tumor development. These opposing anti- and pro-tumorigenic functions are not fully u ... Full text Link to item Cite

Lung inflammation stalls Th17-cell migration en route to the central nervous system during the development of experimental autoimmune encephalomyelitis.

Journal Article Int Immunol · September 2016 Recruiting pathogenic T cells to the central nervous system (CNS) is a critical step during the development of experimental autoimmune encephalomyelitis (EAE). Here, we report that the absence of autophagy and microtubule-associated protein 1A/1B-light cha ... Full text Link to item Cite

Leptin directly promotes T-cell glycolytic metabolism to drive effector T-cell differentiation in a mouse model of autoimmunity.

Journal Article Eur J Immunol · August 2016 Upon activation, T cells require energy for growth, proliferation, and function. Effector T (Teff) cells, such as Th1 and Th17 cells, utilize high levels of glycolytic metabolism to fuel proliferation and function. In contrast, Treg cells require oxidative ... Full text Open Access Link to item Cite

Roles of Autophagy and Autophagy-Related Proteins in Antifungal Immunity.

Journal Article Front Immunol · 2016 Autophagy was initially characterized as a process to digest cellular components, including damaged cell organelles or unused proteins. However, later studies showed that autophagy plays an important role to protect hosts from microbial infections. Accumul ... Full text Link to item Cite

Erratum.

Journal Article Autophagy · 2016 Full text Link to item Cite

Hyperinflammation, T cells, and endotoxemia.

Journal Article Oncotarget · September 15, 2015 Full text Link to item Cite

Calcineurin orchestrates dimorphic transitions, antifungal drug responses and host-pathogen interactions of the pathogenic mucoralean fungus Mucor circinelloides.

Journal Article Mol Microbiol · September 2015 Calcineurin plays essential roles in virulence and growth of pathogenic fungi and is a target of the natural products FK506 and Cyclosporine A. In the pathogenic mucoralean fungus Mucor circinelloides, calcineurin mutation or inhibition confers a yeast-loc ... Full text Link to item Cite

[NLRP3 inflammasome and multiple sclerosis/EAE].

Journal Article Nihon Rinsho · September 2015 Link to item Cite

Cutting edge: Role of osteopontin and integrin αv in T cell-mediated anti-inflammatory responses in endotoxemia.

Journal Article J Immunol · June 15, 2015 Featured Publication The immune system is equipped with mechanisms that downregulate hyperinflammation to avoid collateral damage. We demonstrated recently that unprimed T cells downregulate macrophage TNF production through direct interaction with macrophages in the spleen du ... Full text Link to item Cite

The lung is protected from spontaneous inflammation by autophagy in myeloid cells.

Journal Article J Immunol · June 1, 2015 Featured Publication The lung is constantly exposed to the outer environment; thus, it must maintain a state of immune ignorance or tolerance not to overrespond to harmless environmental stimuli. How cells in the lung control immune responses under nonpathogenic condition is n ... Full text Link to item Cite

Highly Parallel Genome-wide Expression Profiling of Individual Cells Using Nanoliter Droplets.

Journal Article Cell · May 21, 2015 Cells, the basic units of biological structure and function, vary broadly in type and state. Single-cell genomics can characterize cell identity and function, but limitations of ease and scale have prevented its broad application. Here we describe Drop-seq ... Full text Link to item Cite

Neuroinflammation in Alzheimer's disease.

Journal Article Lancet Neurol · April 2015 Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition rec ... Full text Link to item Cite

Autophagy enhances NFκB activity in specific tissue macrophages by sequestering A20 to boost antifungal immunity.

Journal Article Nat Commun · January 22, 2015 Featured Publication Immune responses must be well restrained in a steady state to avoid excessive inflammation. However, such restraints are quickly removed to exert antimicrobial responses. Here we report a role of autophagy in an early host antifungal response by enhancing ... Full text Open Access Link to item Cite

Metabolic programming and PDHK1 control CD4+ T cell subsets and inflammation.

Journal Article J Clin Invest · January 2015 Featured Publication Activation of CD4+ T cells results in rapid proliferation and differentiation into effector and regulatory subsets. CD4+ effector T cell (Teff) (Th1 and Th17) and Treg subsets are metabolically distinct, yet the specific metabolic differences that modify T ... Full text Open Access Link to item Cite

T cells down-regulate macrophage TNF production by IRAK1-mediated IL-10 expression and control innate hyperinflammation.

Journal Article Proc Natl Acad Sci U S A · April 8, 2014 Featured Publication Endotoxemia is caused by excessive inflammation, but the immune system has various mechanisms to avoid collateral organ damage in endotoxemia. A handful of reports have shown that innate immune responses are suppressed by the adaptive immune system. Howeve ... Full text Link to item Cite

Microtubule acetylation amplifies p38 kinase signalling and anti-inflammatory IL-10 production.

Journal Article Nat Commun · March 17, 2014 Featured Publication Reversible acetylation of α-tubulin is an evolutionarily conserved modification in microtubule networks. Despite its prevalence, the physiological function and regulation of microtubule acetylation remain poorly understood. Here we report that macrophages ... Full text Link to item Cite

Clustering of pattern recognition receptors for fungal detection.

Journal Article PLoS Pathog · February 2014 Featured Publication Full text Link to item Cite

The role of interferon-β in the treatment of multiple sclerosis and experimental autoimmune encephalomyelitis - in the perspective of inflammasomes.

Journal Article Immunology · May 2013 Inflammasomes in innate immune cells mediate the induction of inflammation by sensing microbes and pathogen-associated/damage-associated molecular patterns. Inflammasomes are also known to be involved in the development of some human and animal autoimmune ... Full text Link to item Cite

Mnk1 and 2 are dispensable for T cell development and activation but important for the pathogenesis of experimental autoimmune encephalomyelitis.

Journal Article J Immunol · February 1, 2013 Featured Publication T cell development and activation are usually accompanied by expansion and production of numerous proteins that require active translation. The eukaryotic translation initiation factor 4E (eIF4E) binds to the 5' cap structure of mRNA and is critical for ca ... Full text Link to item Cite

NLRP3 Inflammasome and MS/EAE.

Journal Article Autoimmune Dis · 2013 Featured Publication Inflammasomes are cytosolic sensors that detect pathogens and danger signals in the innate immune system. The NLRP3 inflammasome is currently the most fully characterized inflammasome and is known to detect a wide array of microbes and endogenous damage-as ... Full text Link to item Cite

Transcriptional regulator Id2 is required for the CD4 T cell immune response in the development of experimental autoimmune encephalomyelitis.

Journal Article J Immunol · August 1, 2012 An effective immune response to Ag challenge is critically dependent on the size of the effector cell population generated from clonal activation of Ag-specific T cells. The transcription network involved in regulating the size of the effector population, ... Full text Link to item Cite

NLRP3 inflammasome induces chemotactic immune cell migration to the CNS in experimental autoimmune encephalomyelitis.

Journal Article Proc Natl Acad Sci U S A · June 26, 2012 Featured Publication The NLRP3 inflammasome is a multiprotein complex consisting of three kinds of proteins, NLRP3, ASC, and pro-caspase-1, and plays a role in sensing pathogens and danger signals in the innate immune system. The NLRP3 inflammasome is thought to be involved in ... Full text Link to item Cite

Interferon-β therapy against EAE is effective only when development of the disease depends on the NLRP3 inflammasome.

Journal Article Sci Signal · May 22, 2012 Featured Publication Interferon-β (IFN-β) is widely used to treat multiple sclerosis (MS), and its efficacy was demonstrated in the setting of experimental autoimmune encephalomyelitis (EAE), an animal model of MS; however, IFN-β is not effective in treating all cases of MS. H ... Full text Link to item Cite

M-HIFU inhibits tumor growth, suppresses STAT3 activity and enhances tumor specific immunity in a transplant tumor model of prostate cancer.

Journal Article PLoS One · 2012 OBJECTIVE: In this study, we explored the use of mechanical high intensity focused ultrasound (M-HIFU) as a neo-adjuvant therapy prior to surgical resection of the primary tumor. We also investigated the role of signal transducer and activator of transcrip ... Full text Open Access Link to item Cite

Estrogen-related receptor-α is a metabolic regulator of effector T-cell activation and differentiation.

Journal Article Proc Natl Acad Sci U S A · November 8, 2011 Featured Publication Stimulation of resting CD4(+) T lymphocytes leads to rapid proliferation and differentiation into effector (Teff) or inducible regulatory (Treg) subsets with specific functions to promote or suppress immunity. Importantly, Teff and Treg use distinct metabo ... Full text Link to item Cite

Intracellular osteopontin (iOPN) and immunity.

Journal Article Immunol Res · April 2011 Featured Publication Osteopontin (OPN) is a protein involved in various pathophysiological events. OPN has been studied as a secreted protein, but recent reports showed that OPN can be found in the cytoplasm and the nucleus. Therefore, some OPN molecules are not secreted and s ... Full text Link to item Cite

Osteopontin expression during early cerebral ischemia-reperfusion in rats: enhanced expression in the right cortex is suppressed by acetaminophen.

Journal Article PLoS One · January 21, 2011 Osteopontin (OPN) is a pleiotropic protein implicated in various inflammatory responses including ischemia-reperfusion (I-R) injury. Two distinct forms of the protein have been identified: an extensively studied secreted form (sOPN) and a less-well-known i ... Full text Link to item Cite

Cutting edge: critical role of intracellular osteopontin in antifungal innate immune responses.

Journal Article J Immunol · January 1, 2011 Featured Publication We found that absence of osteopontin (OPN) in immunocompromised Rag2(-/-) mice, which lack T and B cells, made the mice extremely susceptible to an opportunistic fungus Pneumocystis, although immunocompetent OPN-deficient mice could clear Pneumocystis as w ... Full text Link to item Cite

Unexpected role of clathrin adaptor AP-1 in MHC-dependent positive selection of T cells.

Journal Article Proc Natl Acad Sci U S A · February 9, 2010 Trafficking of transmembrane receptors to a specific intracellular compartment is conducted by adaptor molecules that bind to target motifs within the cytoplasmic domains of cargo proteins. We generated mice containing a lymphoid-specific deficiency of AP- ... Full text Link to item Cite

Reprogramming after chromosome transfer into mouse blastomeres.

Journal Article Curr Biol · August 25, 2009 It is well known that oocytes can reprogram differentiated cells, allowing animal cloning by nuclear transfer. We have recently shown that fertilized zygotes retain reprogramming activities, suggesting that such activities might also persist in cleavage-st ... Full text Link to item Cite

Regulation of T-helper-cell lineage development by osteopontin: the inside story.

Journal Article Nat Rev Immunol · February 2009 Featured Publication Studies of osteopontin (OPN)-dependent regulation of immune responses have focused on the cytokine activities of the secreted form of this protein. Recent evidence has revealed that an intracellular form of OPN expressed by dendritic cells regulates the ex ... Full text Link to item Cite

Engagement of the type I interferon receptor on dendritic cells inhibits T helper 17 cell development: role of intracellular osteopontin.

Journal Article Immunity · July 18, 2008 Featured Publication Mechanisms that prevent inappropriate or excessive interleukin-17-producing T helper (Th17) cell responses after microbial infection may be necessary to avoid autoimmunity. Here, we define a pathway initiated by engagement of type I IFN receptor (IFNAR) ex ... Full text Link to item Cite

Alternative translation of osteopontin generates intracellular and secreted isoforms that mediate distinct biological activities in dendritic cells.

Journal Article Proc Natl Acad Sci U S A · May 20, 2008 Featured Publication Osteopontin (Opn) contributes to diverse biological processes that include immune responses, vascularization, and bone formation. Until recently, studies describing the activities of Opn have focused on the cytokine-like properties of the secreted protein. ... Full text Link to item Cite

Osteopontin expression is essential for interferon-alpha production by plasmacytoid dendritic cells.

Journal Article Nat Immunol · May 2006 Featured Publication The observation that the T-bet transcription factor allows tissue-specific upregulation of intracellular osteopontin (Opn-i) in plasmacytoid dendritic cells (pDCs) suggests that Opn might contribute to the expression of interferon-alpha (IFN-alpha) in thos ... Full text Link to item Cite

T-bet-dependent expression of osteopontin contributes to T cell polarization.

Journal Article Proc Natl Acad Sci U S A · November 22, 2005 Featured Publication The osteopontin (Opn) glycoprotein has been implicated in diverse physiological processes, including vascularization, bone formation, and inflammatory responses. Studies of its role in immune responses has suggested that Opn can set the early stage of type ... Full text Link to item Cite

Lack of requirement of osteopontin for inflammation, bone erosion, and cartilage damage in the K/BxN model of autoantibody-mediated arthritis.

Journal Article Arthritis Rheum · August 2004 OBJECTIVE: Osteopontin (OPN) is a secreted glycoprotein involved in a range of physiologic processes, including inflammation, immunity mediated by Th1 cells, and bone remodeling. It is expressed in the joints of rheumatoid arthritis patients and has been t ... Full text Link to item Cite

Detailed analysis of gene expression during development of T cell lineages in the thymus.

Journal Article Proc Natl Acad Sci U S A · June 22, 2004 The genetic mechanisms that promote lineage commitment and eliminate autoreactive cells in the thymus are not well understood. To better understand this process, we have identified and quantitated transcripts in the two major thymocyte lineages by using se ... Full text Link to item Cite

Analysis of regulatory CD8 T cells in Qa-1-deficient mice.

Journal Article Nat Immunol · May 2004 The mouse protein Qa-1 (HLA-E in humans) is essential for immunological protection and immune regulation. Although Qa-1 has been linked to CD8 T cell-dependent suppression, the physiological relevance of this observation is unclear. We generated mice defic ... Full text Link to item Cite

Neurospora clock-controlled gene 9 (ccg-9) encodes trehalose synthase: circadian regulation of stress responses and development.

Journal Article Eukaryot Cell · February 2002 Featured Publication The circadian clock of Neurospora crassa regulates the rhythmic expression of a number of genes encoding diverse functions which, as an ensemble, are adaptive to life in a rhythmic environment of alternating levels of light and dark, warmth and coolness, a ... Full text Link to item Cite

A novel thermostable branching enzyme from an extremely thermophilic bacterial species, Rhodothermus obamensis.

Journal Article Appl Microbiol Biotechnol · December 2001 A branching enzyme (EC 2.4.1.18) gene was isolated from an extremely thermophilic bacterium, Rhodothermus obamensis. The predicted protein encodes a polypeptide of 621 amino acids with a predicted molecular mass of 72 kDa. The deduced amino acid sequence s ... Full text Link to item Cite

Comparison of ribosomal DNA ITS regions among geographic isolates of Cenococcum geophilum.

Journal Article Curr Genet · June 1999 Featured Publication Cenococcum geophilum is an ecologically important mycorrhizal fungus with a global distribution and a wide host range. It has been difficult to study since it forms only sterile mycelia and, occasionally, sclerotial bodies. Because of its lack of morpholog ... Full text Link to item Cite

Glyceraldehyde-3-phosphate dehydrogenase is regulated on a daily basis by the circadian clock.

Journal Article J Biol Chem · January 2, 1998 Featured Publication Circadian clocks function to govern a wide range of rhythmic activities in organisms. An integral part of rhythmicity is the daily control of target genes by the clock. Here we describe the sequence and analysis of a novel clock-controlled gene, ccg-7, sho ... Full text Link to item Cite

Circadian clock-controlled genes isolated from Neurospora crassa are late night- to early morning-specific.

Journal Article Proc Natl Acad Sci U S A · November 12, 1996 An endogenous circadian biological clock controls the temporal aspects of life in most organisms, including rhythmic control of genes involved in clock output pathways. In the fungus Neurospora crassa, one pathway known to be under control of the clock is ... Full text Link to item Cite

Group-I intron family in the nuclear ribosomal RNA small subunit genes of Cenococcum geophilum isolates.

Journal Article Curr Genet · March 1996 A family of optional group-I introns was found near the 3' end of the nuclear small subunit rRNA genes in 61 out of 70 isolates of the deuteromycete mycorrhizal fungus Cenococcum geophilum. DNA sequence polymorphisms among the introns (termed CgSSU introns ... Full text Link to item Cite

The genetic and molecular dissection of a prototypic circadian system.

Journal Article Prog Brain Res · 1996 A great deal is known about this archetypal circadian system, and it is likely that Neurospora will represent the first circadian system in which it will be possible to provide a complete description of the flow of information from the photoreceptor, throu ... Full text Link to item Cite

Messenger RNA intron in the nuclear 18s ribosomal RNA gene of deuteromycetes.

Journal Article Curr Genet · 1993 Introns within messenger RNA genes have characteristic border sequences and a conserved region near the 3' end of the intron. All are involved in splicing to produce the mature mRNA. Introns in ribosomal RNA genes have less well-defined borders and contain ... Full text Link to item Cite