Scholars@Duke
Mari L. Shinohara

Mari L. Shinohara

Alter Geller Distinguished Professor for Research in Immunology
Integrative Immunobiology
Box 3010 DUMC, 338 Jones Building, Durham, NC 27710
353 Jones Building, 207 Research Dr., Box 3010 DUMC, Dept of Immunology, Durham, NC 27710

Featured Works

Interplay between fungal infections and autoimmunity: mechanisms and therapeutic perspectives.

Journal article EMBO Mol Med · July 2025 Featured Publication Fungal infections and autoimmunity share a complex, bidirectional relationship that significantly impacts patient outcomes. Emerging evidence highlights how fungal pathogens contribute to autoimmune processes by triggering immune dysregulation. Conversely, ... Full text Link to item 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

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 Open Access Link to item 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

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

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

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

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

Journal article · 2021 Featured Publication ABSTRACT 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 ... Full text 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

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

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 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

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

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

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

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

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

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

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

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

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