The study of the mechanisms of autoimmune systemic vasculitis.

自身免疫性系统性血管炎如显微镜下多动脉炎和过敏性紫癜的病变组织中主要有T细胞和巨噬细胞浸润。在肾脏中，这些免疫细胞在肾小球内和周围以及血管周围的肾小球中观察到。我们发现，在肾脏受累的情况下，尿液中出现了许多与这些浸润肾脏组织具有相同表型的效应型T细胞，并且γδ T细胞参与了肺部疾病的发生。这些效应T细胞表达Th 1细胞因子。这种T细胞的出现是系统性血管炎中器官活跃参与的标志。本研究进一步探讨了IFN-γ在肾小球系膜细胞中的生物学意义，发现信号转导和转录激活因子-1（STAT-1）是一个关键因子，IFN-γ的显性负表达抑制了MHC Ⅱ类分子的表达。 ...更多信息 fSTAT-1在系膜细胞中。在系统性血管炎的晚期肾脏疾病中，肾小管间质损害突出。骨桥蛋白是一种免疫激活剂，在肾小管损伤和再生过程中起重要作用。此外，通过DNA微阵列的全面基因表达分析，MMP-12（巨噬细胞金属酯酶）被确定为肾小球损伤的主要因素。伊加肾病（IgA nephropathy，IgAN）是过敏性紫癜（Schoenlein-Henoch purpura，紫癜）的一种肾脏特异性疾病，通过对200多例患者进行10 ~ 20年的观察，对各种临床资料与基因单核苷酸多态性（single nucleotide polymorphisms，SNPs）的关系进行了统计学分析。IgAN进展的几个候选基因的SNPs与患者的预后相关。扁桃体淋巴细胞在IgAN发病机制中的作用也被强调，扁桃体切除术对IgAN预后的影响也被报道。少

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