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-β1 in a manner dependent on autocrine TGF-β1. By employing IL-17-producing cell-specific Tgfb1 conditional knockout and fate-mapping systems, we demonstrated that TGF-β1-deficient Th17 cells are relatively susceptible to becoming IFN-γ producers through IL-12Rβ2 and IL-27Rα upregulation. TGF-β1-deficient Th17 cells exacerbated tissue inflammation compared to TGF-β1-sufficient Th17 cells in adoptive transfer models of experimental autoimmune encephalomyelitis and colitis. Thus, TGF-β1 production by Th17 cells provides an essential autocrine signal for maintaining the stability and regulating the pathogenicity of Th17 cells in vivo.

Th17 细胞致病性转化为多功能辅助 T 细胞或 Th1 细胞有助于自身免疫性疾病的发病机制；然而，调节 Th17 细胞可塑性的机制仍不清楚。在这里，我们发现 Th17 细胞以依赖于自分泌 TGF-β1 的方式表达潜伏的 TGF-β1。通过使用产生 IL-17 的细胞特异性Tgfb1在条件性敲除和命运映射系统中，我们证明 TGF-β1 缺陷型 Th17 细胞相对容易通过 IL-12Rβ2 和 IL-27Rα 上调而成为 IFN-γ 生产者。在实验性自身免疫性脑脊髓炎和结肠炎的过继转移模型中，与 TGF-β1 充足的 Th17 细胞相比，TGF-β1 缺陷的 Th17 细胞加剧了组织炎症。因此，Th17 细胞产生的 TGF-β1 为维持体内 Th17 细胞的稳定性和调节致病性提供了必要的自分泌信号。