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Mucosal-associated invariant T (MAIT) cells have been implicated in various forms of autoimmunity, including type 1 diabetes (T1D). Here, we tested the hypothesis that CD8 and double negative (DN) MAIT cell frequencies were altered among diagnosed T1D subjects compared to controls. To do this, we analyzed cryopreserved peripheral blood mononuclear...
Multiple environmental triggers have been proposed to explain the increased incidence of type 1 diabetes (T1D). These include viral infections, microbiome disturbances, metabolic disorders, and vitamin D deficiency. Here, we used ELISA to examine blood plasma from juvenile T1D subjects and age-matched controls for the abundance of several circulati...
Interleukin(IL)-4 is produced by T cells and other leukocytes and is a critical mediator of monocyte and B cell responses. During routine flow cytometry panel validation for the investigation of intracellular cytokines, we observed unique IL-4 expression patterns associated with the widely available monoclonal antibody 8D4-8. Namely, IL-4 (8D4-8) e...
We analyzed T cell subsets from cryopreserved PBMC obtained from the TrialNet Pathway to Prevention archives. We compared subjects who had previously seroconverted for one or more autoantibodies with non-seroconverted, autoantibody negative individuals. We observed a reduced frequency of MAIT cells among seroconverted subjects. Seroconverted subjec...
The cytokine interleukin (IL)-18 is a crucial amplifier of natural killer (NK) cell function. IL-18 signaling is regulated by the inhibitory effects of IL-18 binding protein (IL-18BP). Using mice deficient in IL-18BP (IL-18BPKO), we investigated the impact of mismanaged IL-18 signaling on NK cells. We found an overall reduced abundance of splenic N...
Loss of pancreas β-cell function is the precipitating factor in all forms of diabetes. Cell replacement therapies, such as islet transplantation, remain the best hope for a cure; however, widespread implementation of this method is hampered by availability of donor tissue. Thus, strategies that expand functional β-cell mass are crucial for widespre...
Type 1 diabetes (T1D) is a chronic disease characterized by autoimmune-mediated destruction of pancreatic insulin-producing beta cells. Interleukin (IL)-18 is a pro-inflammatory cytokine implicated in the pathogenesis of a number of inflammatory diseases. Here, we analyzed IL-18 levels in the plasma of juveniles with T1D. Compared to control subjec...
Agents that stimulate human pancreatic beta cell proliferation are needed to improve diabetes mellitus treatment. Recently, a small molecule, WS6, was observed to stimulate human beta cell proliferation. However, little is known about its other effects on human islets. To better understand the role of WS6 as a possible beta cell regenerative therap...
Type 1A diabetes (T1D) is believed to be caused by immune-mediated destruction of β-cells, but the immunological basis for T1D remains controversial. Microbial diversity promotes the maturation and activation of certain immune subsets, including CD161bright CD8+ mucosal associated invariant T (MAIT) cells, and alterations in gut mucosal responses h...
Autophagy, a cellular recycling process responsible for turnover of cytoplasmic contents, is critical for maintenance of health. Defects in this process have been linked to diabetes. Diabetes-associated glucotoxicity / lipotoxicity contribute to impaired β-cell function and have been implicated as contributing factors to this disease. We tested the...
Type 1 diabetes (T1D) is a chronic disease caused by autoimmune destruction of insulin-producing pancreatic β-cells. T1D is typically diagnosed in children, but information regarding immune cell subsets in juveniles with T1D is scarce. Therefore, we studied various lymphocytic populations found in the peripheral blood of juveniles with T1D compared...
Toll-like receptors (TLRs) are known to be activated in Central Nervous System (CNS) viral infections and are recognized to be a critical component in innate immunity. Several reports state a role for particular TLRs in various CNS viral infections. However, excessive TLR activation was previously reported by us in correlation with a pathogenic, ra...
In an effort to expand human islets and enhance allogeneic islet transplant for the treatment of type 1 diabetes, identifying signaling pathways that stimulate human beta cell proliferation is paramount. TGF-beta superfamily members, in particular Activin-A, are likely involved in islet development and may contribute to beta cell proliferation. Nod...
Deregulation of DNA repair enzymes occurs in cancers and may create a susceptibility to chemotherapy. Expression levels of DNA repair enzymes have been shown to predict the responsiveness of cancers to certain chemotherapeutic agents. The RECQ helicases repair damaged DNA including damage caused by topoisomerase I inhibitors, such as irinotecan. Al...
Methamphetamine (Meth) is a widely abused stimulant and its users are at increased risk for multiple infectious diseases. To determine the impact of meth on the immune system, we utilized a murine model that simulates the process of meth consumption in a typical addict. Our phenotypic analysis of leukocytes from this dose escalation model revealed...
The mammalian pancreas is required for normal metabolism, with defects in this vital organ commonly observed in cancer and
diabetes. Development must therefore be tightly controlled in order to produce a pancreas of correct size, cell type composition,
and physiologic function. Through negative regulation of Yap-dependent proliferation, the Hippo k...
Type II diabetes is an inflammatory disease marked by chronic immune activation. Our goal is to describe the fundamental distinctions in the immune system of the db/db mouse. Serum was collected for a 58-factor immunoassay. Splenic leukocytes were isolated for six panels of flow cytometry to examine immune subsets and activation states. Db/db mice...
Type 1 diabetes is a disease involving autoimmune destruction of pancreatic beta cells in genetically predisposed individuals. Identifying factors that trigger initiation and progression of autoimmunity may provide opportunities for directed prophylactic and therapeutic measures to prevent and/or treat type 1 diabetes. The human intestinal microbio...
Type 1 diabetes (T1D) is an autoimmune disease that shows familial aggregation in humans and likely has genetic determinants. Disease linkage studies have revealed many susceptibility loci for T1D in mice and humans. The mouse T1D susceptibility locus insulin-dependent diabetes susceptibility 3 (Idd3), which has a homologous genetic interval in hum...
We previously showed that targeted expression of SOCS-1 (Suppressor of Cytokine Signaling-1) to pancreatic beta cells (SOCS-1-transgenic (Tg) islets) from C57BL6/J mice delays islet allograft rejection in BALB/c mice. In the present study, we extend these observations to investigate the mechanism of this delayed rejection. We found that transgene e...
IL-18 has a well-established role in pro-inflammatory responses in the islets in type 1 diabetes. Here, we identify a distinctive role for IL-18 in expanding pathogenic T cells in the periphery of NOD mice. Well in advance of disease onset, the periphery of IL-18-deficient mice exhibits reduced T cell turnover, an increased prevalence of naïve and...
In the NOD mouse, the incidence of type-1 diabetes is thought to be influenced by the degree of cleanliness of the mouse colony. Studies collectively demonstrate that exposure to bacterial antigen or infection in the neonatal period prevents diabetes [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], supporting the notion that immunostimulation can...
The growth and renewal of epithelial tissue is a highly orchestrated and tightly regulated process occurring in different tissue types under a variety of circumstances. We have been studying the process of pancreatic regeneration in mice. We have identified a cell surface protein, named EP1, which is expressed on the duct epithelium during pancreat...
Costimulation via the PD-1 and B7-H1/B7-DC pathway regulates immunity. We investigated whether the PD-1/PD-L pathway is impaired in autoimmune diabetes. A progressive increase in the expression of PD-1 and B7-H1/B7-DC on T cells and APC, respectively, was observed in the pancreatic lymph nodes of female non-obese diabetic (NOD) mice as they develop...
Defects in T cell homeostatic mechanisms can result in T cell lymphopenia, defined as decreased numbers of lymphocytes. Lymphopenia results in homeostatic proliferation in order to maintain T cell homeostasis. It has been proposed that homeostatic proliferation can expand the pool of autoreactive T cells that promote autoimmunity, and indeed recent...
The infiltration of monocytes represents an important early event in the development of autoimmune diabetes in NOD mice. Given that chemokines are key regulators of leukocyte trafficking, we examined the requirement for the chemokine receptors beta(CC)-chemokine receptor-5 (CCR5) and beta(CC)-chemokine receptor-2 (CCR2), which recruit monocytes, in...
Several lines of studies have suggested that activins are critical mediators of inflammation and tissue repair. As activins and their receptors are expressed in the gastrointestinal tract, we tested the hypothesis that activin signaling is involved in the development of colitis by using two murine models of colitis induced by dextran sodium sulfate...
Relative expression of genes involved in glucose-sensing machinery and insulin secretion (b) is not overtly changed in Catnb lox/lox /Cre+ animals. Total RNA waas extracted from total neonatal pancreases. RT quantitative PCR was performed on total pancreas RNA extracts from three mutant and three control (Catnb lox/lox ) animals (Trizol method; Inv...
GLUT2 and PDX1 are produced in islet clusters lacking beta-catenin. Neonatal pancreas sections of control (a–c) and Catnb lox/lox /RIP-Cre + (d–f) were stained with anti-GLUT2 (green), anti-insulin (red) and anti-PDX1 (g, h). c, f Merge of confocal images showing that the neonatal beta cells produced GLUT2 in mutant and in WT mice. Islet clusters d...
Wingless and iNT-1 (WNT) pathway members are critical for pancreatic development and exocrine tissue formation. Recently, much attention has focused on delineating the roles of beta-catenin in pancreatic organogenesis. However, little is known about the involvement of beta-catenin in the endocrine or exocrine function of the mature pancreas. We rep...
Inhibitors of DNA binding proteins (Ids) are implicated in the control of proliferation and differentiation. Herein, we tested the hypothesis that Id2 could stimulate proliferation and survival in differentiated pancreatic beta cells. We showed that Id2-enhanced proliferation of a growth-arrested pancreatic beta cell line (BTC-tet). This was mediat...
Several key transcription factors are necessary for alpha cell development in the pancreas. In this study, we describe the expression of Inhibition of DNA-binding protein 1 (Id1) in the developing as well as the normal adult pancreas. We found co-expression of Id1 with bone morphogenetic protein (BMP) receptor in alpha cells. Inhibition of BMP4 sig...
Fibroblast growth factors (FGFs) are important regulators of the dynamic development and turnover of tissues. Among FGF receptors, FGFR3 expression is confined in the intestinal crypts. We examined FGFR3-deficient mice and saw increased intestinal crypt depth but no change in villae length or in the distribution of differentiated intestinal cells,...
Despite recent scientific advances, the mechanisms inducing neuronal death in many human brain diseases remain unknown. Selective
neuronal vulnerability, often with slowly developing loss of neurons, is a common feature of neurodegenerative disorders,
infectious CNS diseases and their postinfectious states, certain forms of epilepsy, and hypoxic in...
Nodal and its antagonist, Lefty, are important mediators specifying the laterality of the organs during embryogenesis. Nodal signals through activin receptors in the presence of its co-receptor, Cripto. In the present study, we investigated the possible roles of Nodal and Lefty signaling during islet development and regeneration. We found that both...
Non‐obese diabetic (NOD) mice have been characterized as lymphopenic and undergo homeostatic proliferation, leading to the generation of auto‐reactive T cells. In addition, previous work has shown that NOD mice have increased expression of the common γ‐binding cytokine, IL‐21, and its receptor, IL‐21R. To investigate whether IL‐21 is responsible fo...
Interleukin‐18 (IL‐18) has a well‐established role in promoting type 1 cytokine responses in autoimmunity and inflammation. Here, using non‐obese diabetic (NOD) mice that are genetically deficient in IL‐18 (IL‐18KO NOD), we have identified a role for IL‐18 in regulating intra‐thymic T cell differentiation that was associated with constitutive IL‐18...
Type 1 diabetes results from destruction of insulin‐producing pancreatic beta cells. A possible treatment is to replace these cells by genetic engineering or the use of stem cells. This approach requires that we understand the signals that regulate beta cell proliferation. Inhibition of DNA binding proteins (Ids), are implicated in a number of cell...
Nodal and its antagonist, Lefty, are important mediators specifying the laterality of the organs during embryogenesis. Nodal signals through activin receptors in the presence of its co‐receptor, Cripto. In the present study, we investigated the possible roles of Nodal and Lefty signaling during islet development and islet regeneration. By using imm...
IL-21, a member of the common gamma-chain utilizing family of cytokines, participates in immune and inflammatory processes. In addition, the cytokine has been linked to autoimmunity in humans and rodents.
To investigate the mechanism whereby IL-21 affects the immune system, we investigated its role in T cell homeostasis and autoimmunity in both non...
The absence of B7-2-mediated costimulation protects NOD mice from the development of diabetes. Although the effects of B7-2 on T cell priming are well known, its impact on the function of APCs is not fully elucidated. We tested APC function and survival in mice lacking B7-2. A significant reduction in the phagocytic ability was observed in both spl...
Costimulation by B7-1 and B7-2 molecules results in divergent biological effects. This is particularly striking in the NOD mouse, since the lack of B7-2 leads to complete protection from diabetes whereas the B7-1 deficiency causes exacerbation of disease. We tested the hypothesis that B7-1 costimulation suppresses pancreatic autoimmunity. We descri...
Costimulation via the PD-1/PD-L and B7/CD28 pathways modulates immune response towards self/non-self. We investigated whether the PD-1/PD-L pathway is impaired in autoimmune diabetes. Secondly, we hypothesized that B7-2 affects antigen presenting cell (APC) function. A progressive increase in the proportion of PD-1, B7-H1 and B7-DC positive T cells...
Central and peripheral tolerance mechanisms were for a long time the only regulatory circuits known in autoimmunity. It is now becoming clear that the target tissue itself may have the capacity to control its own destiny. Here we review mechanisms by which the target tissue regulates local inflammation, and the way this could influence progression...
The absence of diabetes in NOD mice devoid of B7-2 signifies a critical role played by B7-2 in promoting autoimmunity. We asked whether the CD8 T cell compartment is impacted by the absence of B7-2. We found significantly lower expansion of anti-islet CD8 T cells in B7-2KO mice, although their survival and activation states remained unchanged in th...
IL-4 is protective against Type 1 diabetes in the NOD mouse. IL-4 promotes T cell survival in vitro, but little is known about the effect of IL-4 on clonal expansion in vivo. Here, we show that IL-4 only enhances the expansion of autoreactive CD4 T cells during lymphopenia and that neither the presence of islet IL-4 nor IL-4 deficiency affects T ce...
Signaling pathways play critical roles in most physiological and pathological processes and convert an extracellular stimulus into a change of function in the recipient cell. Intracellular messages originate from the activation of membrane receptors by a variety of ligands, such as hormones, nutrients or growth factors. The receptors subsequently i...
Type 1 diabetes occurs when self-reactive T lymphocytes destroy the insulin-producing islet β cells of the pancreas. The defects causing this disease have often been assumed to occur exclusively in the immune system. We present evidence that genetic variation at the Idd9 diabetes susceptibility locus determines the resilience of the targets of auto...
Fibroblast growth factors (FGFs) and their receptors (FGFRs) are key signaling molecules for pancreas development. Although FGFR3 is a crucial developmental gene, acting as a negative regulator of bone formation, its participation remains unexplored in pancreatic organogenesis. We found that FGFR3 was expressed in the epithelia in both mouse embryo...
Chimerism data for the experiment in Figure 3D. This figure shows the %Thy1.1+ cells within CD4 and CD8 T cell populations for secondary lymphoid organs in irradiated Idd9 (circles) and NOD (filled diamonds) recipients. No difference in %Thy1.1 (donor) cells between Idd9 congenic and NOD recipients is observed.
Gut peptide YY (PYY) plays an important role in regulating metabolism and is expressed during the ontogeny of the pancreas. However, its biological role during endocrine cell formation is not fully understood, and its role, if any, during pancreatic regeneration in the adult has not yet been explored. The knowledge of factors involved in beta cell...
Inhibitor of DNA binding (Id) proteins bind to and inhibit the function of basic helix-loop-helix (bHLH) transcription factors including those that regulate pancreatic development. Moreover, bone morphogenetic proteins (BMPs) regulate the expression of Ids. We hypothesized that BMP4 and Id proteins play a role in the expansion and differentiation o...
T cell activation is a complex process that requires a multitude of interactions between antigen-presenting cells (APC) and T cells. The primary signal is provided via the binding of the antigen (Ag) presented by the major histocompatibility complex (MHC) on an APC and the T cell receptor (TCR). This signal determines the specificity of the immune...
Clinical myocarditis is a precursor to dilated cardiomyopathy and a principal cause of heart failure. Nearly 30% of all recently diagnosed cases of myocarditis are attributable to infection with coxsackie B virus (CBV), the most frequently associated pathogen. CBV initially replicates in the pancreas and quickly spreads to the heart, inducing chron...
The major cell fate decision of the CD4+ helper T cells is the development of Th1 and Th2 phenotype, the balance of which determines the outcome of a wide variety of autoimmune responses. Signal transducers and activators of transcription (STATs), in particular STAT4 and STAT6, are essential for the development of Th1 and Th2 cells, respectively. W...
Chronic myocarditis often progresses to dilated cardiomyopathy resulting in heart failure or cardiac transplantation. Viral infection is the most common cause of myocarditis and coxsackie B viruses (CBV) are the most frequently cited etiologic agents associated with myocarditis and cardiomyopathy. Additionally, CBV infections of genetically suscept...
The size of the peripheral T cell pool is remarkably stable throughout life, reflecting precise regulation of cellular survival, proliferation, and apoptosis. Homeostatic proliferation refers to the process by which T cells spontaneously proliferate in a lymphopenic host. The critical signals driving this expansion are "space," contact with self-ma...
Although candidate genes controlling autoimmune disease can now be identified, a major challenge that remains is defining the resulting cellular events mediated by each locus. In the current study we have used NOD-InsHA transgenic mice that express the influenza hemagglutinin (HA) as an islet Ag to compare the fate of HA-specific CD8+ T cells in di...
The ability to block interferon signaling represents an important strategy in designing therapies to prevent beta-cell destruction during islet allograft rejection.
The SOCS proteins regulate cytokine signaling by blocking activation of JAK/STAT proteins. Using islets isolated from SOCS-1 transgenic mice (SOCS-1-Tg; these mice express SOCS-1 under...
Activated signaling proteins regulate diverse processes, including the differentiation of the pancreatic islet cells during ontogeny. Here we uncover the in vivo phosphorylation status of major growth factor-activated signaling proteins in normal adult mice and during pancreatic islet regeneration. We report elevated phospho-mitogen-activated prote...
Pancreatic islet transplantation represents an attractive approach for the treatment of diabetes. However, the limited availability of donor islets has largely hampered this approach. In this respect, the use of alternative sources of islets such as the ex vivo expansion and differentiation of functional endocrine cells for treating diabetes has be...
Coxsackievirus (CV) is an important human pathogen that has been linked to the development of autoimmunity. An intact pancreatic beta cell IFN response is critical for islet cell survival and protection from type 1 diabetes following CV infection. In this study, we show that IFNs trigger an antiviral state in beta cells by inducing the expression o...
NOD mice spontaneously develop insulitis and type 1 diabetes (T1D) mellitus similar to humans. Insulitis without overt disease occurs in the BDC2.5 TCR-transgenic NOD mice that express the rearranged TCR alpha- and beta-chain genes of a diabetogenic T cell clone reactive to an unknown beta cell autoantigen. A previous study identified an extensive...
The B7-1/2-CD28 system provides the critical signal for the generation of an efficient T cell response. We investigated the role played by B7-2 in influencing pathogenic autoimmunity from islet-reactive CD4 T cells in B7-2 knockout (KO) NOD mice which are protected from type 1 diabetes. B7-2 deficiency caused a profound diminishment in the generati...
Cross-reactivity between an autoantigen and unknown microbial epitopes has been proposed as a molecular mechanism involved in the development of insulin-dependent diabetes (type 1 diabetes). Type 1 diabetes is an autoimmune disease that occurs in humans and the nonobese diabetic (NOD) mouse. BDC2.5 is an islet-specific CD4+ T-cell clone derived fro...
Activins regulate the growth and differentiation of a variety of cells. During pancreatic islet development, activins are required for the specialization of pancreatic precursors from the gut endoderm during midgestation. In this study, we probed the role of activin signaling during pancreatic islet cell development and regeneration. Indeed, we fou...
The immunoregulatory function of NKT cells is crucial for prevention of autoimmunity. The prototypical NKT cell Ag alpha-galactosylceramide is not present in mammalian cells, and little is known about the mechanism responsible for NKT cell recruitment and activation. Up-regulation of CD1d, the NKT cell restriction molecule, expressed on mononuclear...
During illness and stress, the immune system can suffer a considerable loss of T cells (lymphopenia). The remaining T cells undergo vigorous compensatory expansion, known as homeostatic proliferation, to reconstitute the immune system. Interestingly, human diseases of autoimmune etiology often present with immune deficiencies such as lymphopenia. I...
The wide diversity of the T and B Ag receptor repertoires becomes even more extensive postneonatally due to the activity of TdT, which adds nontemplated N nucleotides to Ig and TCR coding ends during V(D)J recombination. In addition, complementarity-determining region 3 sequences formed in the absence of TdT are more uniform due to the use of short...
Natural killer (NK) cells are the first line of defense against infection and transformation. Additionally, NK cells can play seemingly opposite roles in autoimmune disease. Here, we summarize the functions of NK cells as both regulators and inducers of autoimmune disease. The role NK cells play depends on which cells become targets for NK cell att...
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is frequently used in preclinical and clinical protocols to modulate autoimmune responses, bone marrow transplants, and recovery from immune ablative therapies. The immunological outcome of such therapies is not fully understood. We tested the hypothesis that GM-CSF would enhance the maturat...
Epidemiological studies have associated coxsackie B virus (CBV) with the development of insulin-dependent diabetes mellitus (IDDM) in humans. Infections of genetically susceptible mice with CBV strain 4 (CB4) induce autoimmune diabetes. Herein, we demonstrate that in mice, CB4 infection of insulin-producing pancreatic beta cells does not directly c...
This chapter discusses the origin of the nonobese diabetic (NOD) mouse, the pathogenesis of diabetes, and the role of the immune cells in pathogenesis and some of the important discoveries that have facilitated and expanded the understanding of both immunity and autoimmunity. With the development of spontaneous diabetes, the NOD mouse shares many p...
Cytokines are critical mediators in autoimmunity and a better understanding of their mode of action should contribute to the development of strategies for controlling harmful autoimmune reactions. Their complicated nature makes it difficult to classify them as pro- or anti-inflammatory mediators; redundancy in their mode of action has been widely r...
he SDF-1 � /CXCR4 ligand/chemokine receptor pair is required for appropriate patterning during ontogeny and stimulates the growth and differentiation of critical cell types. Here, we demonstrate SDF-1 � and CXCR4 expression in fetal pancreas. We have found that SDF-1 � and its receptor CXCR4 are expressed in islets, also CXCR4 is expressed in and a...
Although lymphocyte infiltration and islet destruction are hallmarks of diabetes, the mechanisms of beta-cell destruction are not fully understood. One issue that remains unresolved is whether cytokines play a direct role in beta-cell death. We investigated whether beta-cell cytokine signaling contributes to autoimmune type 1 diabetes. We demonstra...
The induction of autoimmunity by viruses has been hypothesized to occur by a number of mechanisms. Coxsackievirus B4 (CB4) induces hyperglycemia in SJL mice resembling diabetes in humans. While virus is effectively cleared within 2 weeks, hyperglycemia does not appear until about 8-12 weeks postinfection at a time when replicative virus is no longe...
Diabetes mellitus results from the anatomical or functional loss of insulin-producing beta cells of the pancreas. Despite significant advances in current treatment, patients with diabetes still do not maintain optimal glucose levels and therefore face debilitating complications such as hypoglycemia, retinopathy or cardiovascular diseases later in l...
Pancreatic beta-cell antiviral defense plays a critical role in protection from coxsackievirus B4 (CVB4)-induced diabetes. In the present study, we tested the hypothesis that interferon (IFN)-induced antiviral defense determines beta-cell survival after infection by the human pathogen CVB3, cytomegalovirus (CMV), and lymphocytic choriomeningitis vi...
The control of lymphocyte recruitment to the site of inflammation is an important component determining the pathogenicity of an autoimmune response. Progression from insulitis to diabetes in the nonobese diabetic mouse is typically associated with Th1 pancreatic inflammation, whereas Th2 inflammation can seemingly be controlled indefinitely. We sho...
Chemokine receptor expression is exquisitely regulated on T cell subsets during the course of their migration to inflammatory sites. In the present study we demonstrate that CCR4 expression marks a pathogenic population of autoimmune T cells. CCR4 was found exclusively on memory CD4(+) T cells during the progression of disease in NOD mice. Cells ex...
Cytokines are the co-ordinators of the immune system and, as such, are important targets for immunomodulation. Progress has been made towards the use of IL-10 for immunosuppressive therapy to prevent autoimmunity. Interest has also recently focused on the role of cytokines in controlling the activation of dendritic cells and NK cells, and the conse...
We have recently shown that leptin, the product of the obese gene, can directly influence T-cell function. In the work presented here, we explored the role of leptin in the development of spontaneous autoimmunity in the nonobese diabetic (NOD) mouse, an animal model for the study of human insulin-dependent diabetes mellitus (type 1 diabetes). We fo...
Autoimmune diseases are chronic conditions resulting from a loss of immunological tolerance to self-antigens. Recent observations have supported an ever-broader role for innate immune responses in directing and regulating adaptive immunity, including responses to self. This review summarizes recent findings supporting important functions of natural...
