The study of the mechanisms of autoimmune systemic vasculitis.

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T cells and macrophages predominantly infiltrate in diseased tissues of autoimmune systemic vasculitis such as microscopic polyarteritis and Schoenlein-Henoch purpura. In kidneys these immune cells are observed in and around glomeruli, and in the interstitium around vessels. We revealed that many effector-type T cells, which had the same phenotype as these infiltrating kidney tissues, appeared in urine in case of renal involvement, and that γδ T cells were involved in the development of lung diseases. These effector T cells expressed Th1 cytokines. The appearance of such T cells is a hallmark of active involvement of the organs in systemic vasculitis. Then we focused on the biological significance of IFN-γ and investigated the signaling mechanisms in mesangial cells which is a renal resident of glomerular capillary.We showed that STAT-1 (signal transducer and activator of transcription-1) was a key factor, and that MHC classII expression was suppressed by dominant negative expression o … More f STAT-1 in mesangial cells. In advanced forms of renal diseases of systemic vasculitis tubulointerstitial damage is prominent. An immunological activator, Osteopontin, was revealed to play an important role in the process of tubular damage and regeneration. In addition, through a comprehensive gene expression analysis with DNA microarray, MMP-12 (macrophage metalloesterase) was identified as a major factor for glomerular injury. As for IgA nephropathy (IgAN) which is considered as a kidney specific form of Schoenlein-Henoch purpura, more than 200 patients who were observed for 10 to 20 years were statistically examined by investigation of relationship between various clinical data and single nucleotide polymorphisms (SNPs) of genes. SNPs of several candidate genes for the progression of IgAN was associated with the prognosis of the patients. The role of tonsilar lymphocytes in the pathogenesis of IgAN was also highlighted and the effect of tonsillectomy on the prognosis of IgAN was reported. Less