Purpose of review: 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 findings: 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.
Summary: 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.