A5026873284- Liver Diseases and Immunity
- Diabetes and associated disorders
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Liver Disease Diagnosis and Treatment
- Liver physiology and pathology
- Pancreatic function and diabetes
- Inflammatory Bowel Disease
- Diabetes Management and Research
- Pediatric Hepatobiliary Diseases and Treatments
- Immunotherapy and Immune Responses
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Immunodeficiency and Autoimmune Disorders
- Systemic Lupus Erythematosus Research
- Galectins and Cancer Biology
- Cytokine Signaling Pathways and Interactions
- IL-33, ST2, and ILC Pathways
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Macrophage Migration Inhibitory Factor
- Immune Response and Inflammation
- Immune cells in cancer
- Inflammatory Myopathies and Dermatomyositis
- Long-Term Effects of COVID-19
- Celiac Disease Research and Management
- Glycosylation and Glycoproteins Research
University of California, Davis
2020-2024
University of Cincinnati Medical Center
2010-2022
VA Northern California Health Care System
2022
Sacramento VA Medical Center
2022
University of Cincinnati
2008-2019
University of Pittsburgh
1999-2008
Center for Rheumatology
2004-2006
Stanford University
1993-1999
University Foundation
1913
Experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, is disorder seen in mice and rats following immunization with myelin basic protein (MBP) or MBP-derived peptides. IFN-gamma, a cytokine produced by variety of cells, involved many inflammatory immune regulatory events. Contradictory results concerning exacerbations the disease course were comparing injections IFN-gamma humans suffering from sclerosis to studies using anti-IFN-gamma Abs EAE. To study role...
Abstract Primary biliary cirrhosis (PBC) is an autoimmune disease of the liver, characterized by lymphocytic infiltrates in portal tracts, selective destruction epithelial cells, and anti-mitochondrial Abs (AMAs). The elucidation early events induction tissue inflammation autoimmunity PBC has been hampered cryptic onset disease, practical limitations accessing target tissue, lack a suitable animal model. We demonstrate this study that mouse transgenic for directed expression...
Humans with primary biliary cirrhosis (PBC), a disease characterized by the destruction of small bile ducts, exhibit signature autoantibodies against mitochondrial Pyruvate Dehydrogenase Complex E2 (PDC-E2) that crossreact onto homologous enzyme Novosphingobium aromaticivorans, an ubiquitous alphaproteobacterium. Here, we show infection mice N. aromaticivorans induced antibodies microbial PDC-E2 and its counterpart but also triggered chronic T cell-mediated autoimmunity ducts. Disease...
Recently, we identified a child born with genetic deficiency of IL-2 receptor α (IL-2Rα, CD25) expression who had several clinical manifestations primary biliary cirrhosis (PBC). In addition, there has been suggestive evidence in both patients PBC and their first-degree relatives that regulatory T cells (Tregs) is an integral component for susceptibility to PBC. Based on these observations, generated IL-2Rα/CD25 deficient (IL-2Rα−/−) mice wild-type littermate controls followed them...
Primary biliary cirrhosis (PBC) is an autoimmune disease with a strong genetic component characterized by ductular inflammation eventual liver cirrhosis. The serologic hallmark of PBC antimitochondrial antibodies that react the pyruvate dehydrogenase complex, targeting inner lipoyl domain E2 subunit (anti–PDC-E2). Herein we demonstrate NOD.c3c4 mice congenically derived from nonobese diabetic strain develop (ABD) models human PBC. (at 9–10 wk, before significant pathology) to PDC-E2 are...
There have been important advances in defining effector mechanisms for several human autoimmune diseases. However, most diseases, the induction stage is less well defined and there are very few clues on etiology. Our laboratory has focused molecular basis of autoantibody recognition epitope modification primary biliary cirrhosis (PBC). work demonstrated that antibodies to mitochondria, hallmark disease, directed against a conserved site pyruvate dehydrogenase, E2 subunit dehydrogenase...
We recently reported that mice with a T cell–restricted expression of dominant negative form transforming growth factor β receptor type II (dnTGFβRII) spontaneously develop autoimmune cholangitis resembles human primary biliary cirrhosis (PBC), including antimitochondrial antibodies (AMAs) and extensive portal CD4+ CD8+ lymphocytic infiltrates. On the basis these data, we performed series experiments to determine whether pathology was secondary direct dnTGFβRII disruption liver and/or...
Mice with a dominant-negative transforming growth factor β receptor restricted to T cells (dnTGFβRII mice) develop an inflammatory biliary ductular disease that strongly resembles human primary cirrhosis (PBC). Furthermore, deletion of the gene encoding interleukin (IL)-12p40 resulted in strain (IL-12p40−/−dnTGFβRII) dramatically reduced autoimmune cholangitis. To further investigate role IL-12 cytokine family dnTGFβRII disease, we deleted IL-12p35 subunit from mice, resulting IL-12p35−/−...
Individuals with autoimmune diseases show a preponderance of certain types major histocompatibility complex (MHC) molecule. It has usually been assumed that this is because these MHC molecules bind the autoantigens associated disease more efficiently than they other antigens. In their Perspective, Ridgway et al. propose another explanation for association-these are poor at screening out when immune system first defined in thymus.
Primary biliary cirrhosis (PBC) is an organ-specific autoimmune liver disease characterized by the presence of antimitochondrial antibodies and destruction small intrahepatic bile ducts with portal inflammation. In previous studies, we reported that both CD1d expression frequency CD1d-restricted natural killer T (NKT) cells were increased in livers patients PBC. To define a specific role NKT pathogenesis PBC, particularly early events, investigated function hepatic our transforming growth...
Summary Our laboratory has suggested that loss of tolerance to pyruvate dehydrogenase (PDC-E2) leads an anti-mitochondrial antibody response and autoimmune cholangitis, similar human primary biliary cirrhosis (PBC). We have this can be induced either via chemical xenobiotic immunization or exposure select bacteria. work also highlighted the importance genetic susceptibility. Using non-obese diabetic (NOD) congenic strain 1101 (hereafter referred as NOD.1101 mice), which chromosome 3 regions...
Interleukin-2 (IL-2) receptor α knockout (IL-2Rα−/−) mice have a deficiency of CD25 and corresponding functional defect in T regulatory cells (Tregs). These spontaneously develop portal inflammation with biliary ductular damage colitis features similar to human inflammatory bowel disease cell infiltrates both the liver colon. In humans, may be accompanied by primary sclerosing cholangitis (PSC), but seldom cirrhosis (PBC). We hypothesized that effector mechanism responsible for would differ...
Several epidemiological studies have demonstrated that patients with primary biliary cirrhosis (PBC) a higher incidence of urinary tract infections (UTI) and there is significant homology the immunodominant mitochondrial autoantigen, E2 component pyruvate dehydrogenase complex (PDC-E2), between mammals bacteria. Previous work has non-obese diabetic (NOD).B6 Idd10/Idd18 infected Novosphingobium aromaticivorans developed liver lesions similar to human PBC. It was postulated disease dependent...
Abstract At least 20 insulin-dependent diabetes (Idd) loci modify the progression of autoimmune in NOD mouse, an animal model human type 1 diabetes. The NOD.c3c4 congenic which has multiple B6- and B10-derived Idd-resistant alleles on chromosomes 3 4, respectively, is completely protected from We demonstrate this study, however, that mice develop a novel spontaneous fatal polycystic biliary tract disease, with lymphocytic peribiliary infiltrates autoantibodies. Strains having subset present...