Ragon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Harvard Medical School, Cambridge, Massachusetts, USA.
Curr Opin Rheumatol. 2019 Nov;31(6):576-581. doi: 10.1097/BOR.0000000000000644.
To summarize recent advances in the understanding of the pathogenesis of autoimmune fibrotic diseases. These diseases include IgG4-related disease, systemic sclerosis and lupus nephritis.
Recent studies indicate that a poorly studied subset of helper T cells, cytotoxic CD4+ T cells and sub-populations of disease-specific activated B cells infiltrate inflamed tissues and collaborate to induce tissue fibrosis in autoimmune fibrotic diseases. Cycles of apoptosis induced by antigen-specific cytotoxic CD4+ T cells followed by macrophage-mediated clearing of apoptotic cells and finally tissue remodeling driven by cytokines released by these auto-antigen-specific activated T and B cells may contribute to the activation of fibroblasts and myofibroblasts and the laying down of collagen. In scleroderma, this process likely involves the apoptosis of endothelial cells and other neighboring cells and the subsequent remodeling of the tissue.
Self-reactive cytotoxic CD4+ T cells infiltrate tissues where they may be nurtured by activated auto-reactive B cells, induce apoptosis, secrete cytokines and thus drive autoimmune fibrosis.
总结自身免疫性纤维性疾病发病机制研究的最新进展。这些疾病包括 IgG4 相关疾病、系统性硬化症和狼疮性肾炎。
最近的研究表明，辅助性 T 细胞、细胞毒性 CD4+T 细胞和疾病特异性激活 B 细胞的一个研究较少的亚群浸润到炎症组织中，并协同诱导自身免疫性纤维性疾病中的组织纤维化。抗原特异性细胞毒性 CD4+T 细胞诱导的细胞凋亡、随后由巨噬细胞清除凋亡细胞，最后由这些自身抗原特异性激活的 T 和 B 细胞释放的细胞因子驱动的组织重塑，可能导致成纤维细胞和肌成纤维细胞的激活以及胶原蛋白的沉积。在硬皮病中，这个过程可能涉及内皮细胞和其他邻近细胞的凋亡，以及随后的组织重塑。
自身反应性细胞毒性 CD4+T 细胞浸润到组织中，在那里它们可能被激活的自身反应性 B 细胞滋养，诱导细胞凋亡，分泌细胞因子，从而驱动自身免疫性纤维化。
