A critical role for Th17 cell-derived TGF-β1 in regulating the stability and pathogenicity of autoimmune Th17 cells

Pathogenic conversion of Th17 cells into multifunctional helper T cells or Th1 cells contributes to the pathogenesis of autoimmune diseases; however, the mechanism regulating the plasticity of Th17 cells remains unclear. Here, we found that Th17 cells expressed latent TGF-beta 1 in a manner dependent on autocrine TGF-beta 1. By employing IL-17-producing cell-specific Tgfb1 conditional knockout and fate-mapping systems, we demonstrated that TGF-beta 1-deficient Th17 cells are relatively susceptible to becoming IFN-gamma producers through IL-12R beta 2 and IL-27R alpha upregulation. TGF-beta 1-deficient Th17 cells exacerbated tissue inflammation compared to TGF-beta 1-sufficient Th17 cells in adoptive transfer models of experimental autoimmune encephalomyelitis and colitis. Thus, TGF-beta 1 production by Th17 cells provides an essential autocrine signal for maintaining the stability and regulating the pathogenicity of Th17 cells in vivo. Autoimmune disease: Transforming growth factor keeps subset of T cells in check A protein secreted by pro-inflammatory immune cells acts on the same secreting cells to prevent their conversion into pathogenic drivers of autoimmune disease. A team in South Korea led by Byung-Seok Kim from Incheon National University and Yeonseok Chung from Seoul National University showed that T helper 17 (Th17) cells, a subset of T helper cells defined by their production of a signaling molecule known as interleukin 17, express a protein called transforming growth factor-beta 1 (TGF-beta 1) that maintains the stability of Th17 in a self-regulating manner. Without the ability to produce TGF-beta 1, the cells tend to convert into a form that fuel disease-associated inflammation in mouse models of multiple sclerosis and colitis. Therapeutic blockade of this conversion process could help treat diseases linked to Th17 cell-mediated autoimmunity.