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A major target autoantigen in anti-neutrophil cytoplasmic antibody-associated vasculitis is myeloperoxidase (MPO). Although MPO-specific CD4+ Th cells seem to orchestrate renal injury, the role of the Th17 subset is unknown. We hypothesized that Th17 cells direct injurious anti-MPO autoimmunity in experimental murine anti-MPO-induced glomerulonephritis(More)
Mast cells contribute to the modulation of the immune response, but their role in autoimmune renal disease is not well understood. Here, we induced autoimmunity resulting in focal necrotizing GN by immunizing wild-type or mast cell-deficient (Kit(W-sh/W-sh)) mice with myeloperoxidase. Mast cell-deficient mice exhibited more antimyeloperoxidase CD4+ T cells,(More)
The expression pattern of proinflammatory cytokines, neuronal nitric oxide synthase (nNOS), substance P (SP) and calcitonin gene related peptide (CGRP) in the spinal cord and the bladder in response to permanent middle cerebral artery occlusion (MCAO) was investigated. In this connection, the gene expression of tumor necrosis factor alpha (TNF-alpha),(More)
Antimyeloperoxidase antibodies can cause crescentic glomerulonephritis and pulmonary hemorrhage. Toll-like receptors (TLRs) respond to infectious agents activating host defenses, whereas infections potentially initiate disease and provoke relapses. Neutrophils were found to be key effector cells of injury in experimental models, as disease does not occur in(More)
Cytokines play an important role in host defense against microorganisms. They orchestrate innate immunity by inducing protective local inflammation and systemic acute phase responses. Cytokines are important in initiating, amplifying, directing, mediating, and regulating adaptive immunity. Unfortunately, they may also direct tissue damage if excessive(More)
Observations in experimental murine myeloperoxidase (MPO)-ANCA-associated vasculitis (AAV) show mast cells degranulate, thus enhancing injury as well as producing immunomodulatory IL-10. Here we report that, compared with biopsy specimens from control patients, renal biopsy specimens from 44 patients with acute AAV had more mast cells in the interstitium,(More)
OBJECTIVE Autoantibodies constitute the hallmark of antineutrophil cytoplasmic antibody-associated vasculitis (AAV); however, CD4+ T cells play an essential role in the development of autoimmunity. Infection is associated with vasculitis, with Toll-like receptors (TLRs) a potential link between infection and autoimmunity. This study was undertaken to(More)
T helper (Th)17 cells might contribute to immune-mediated renal injury. Thus, we sought to define the time course of IL-17A-induced kidney damage and examined the relation between Th17 and Th1 cells in a model of crescentic anti-glomerular basement membrane glomerulonephritis. Renal injury and immune responses were assessed in wild-type and in(More)
Although Th17 responses may contribute to the pathogenesis of glomerulonephritis, whether the key transcription factor in Th17 cell development, RORγt, also promotes glomerulonephritis is unknown. Here, we induced crescentic glomerulonephritis in wild-type and RORγt-deficient (RORγt(-/-)) mice. RORγt(-/-) mice were protected from disease, with reduced(More)
Progressive renal fibrosis is the final common pathway leading to renal failure irrespective of the initiating cause. Clinical studies of renal fibrosis found that prominent mast cell accumulation correlated with worse outcomes. Mast cells are pluripotent innate immune cells that synthesize and secrete profibrotic mediators. Here we use mast cell-deficient(More)