Transforming growth factor beta 1 (TGF-β1) is an immunosuppresive cytokine that plays an essential role in immune homeostasis. It is well known that regulatory T (Treg) cells express TGF-β1; however, the role of autocrine TGF-β1 in the development, function, and stability of Treg cells remains poorly understood. We found that Treg cell-derived TGF-β1 was not required for the development of thymic Treg cells in mice, but played a role in the expression of latency-associated peptide and optimal suppression of naïve T cell proliferation in vitro. Moreover, the frequency of Treg cells was significantly reduced in the mesenteric lymph nodes of the Treg cell-specific TGF-β1-deficient mice, which was associated with increased frequency of IFN-γ-producers among Treg cells. TGF-β1-deficient Treg cells were more prone to express IFN-γ than TGF-β1-sufficient Treg cells in a dendritic cell-mediated stimulation in vitro as well as in an adoptive transfer study in vivo. Mechanistically, TGF-β1-deficient Treg cells expressed higher levels of Il12rb2 and were more sensitive to IL-12-induced conversion into IFN-γ-producing Treg cells or IFN-γ-producing exTreg cells than TGF-β1-sufficient Treg cells. Our findings demonstrate that autocrine TGF-β1 plays a critical role in the optimal suppressive activity and stability of Treg cells by downregulating IL-12R on Treg cells.

中文翻译：

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自分泌 TGF-β1 通过 IL-12Rβ2 下调维持 Foxp3+ 调节性 T 细胞的稳定性。


转化生长因子β1 (TGF-β1) 是一种免疫抑制细胞因子，在免疫稳态中发挥重要作用。众所周知，调节性 T (Treg) 细胞表达 TGF-β1；然而，自分泌 TGF-β1 在 Treg 细胞的发育、功能和稳定性中的作用仍知之甚少。我们发现，Treg 细胞衍生的 TGF-β1 并不是小鼠胸腺 Treg 细胞发育所必需的，但在潜伏相关肽的表达和体外最佳抑制幼稚 T 细胞增殖中发挥了作用。此外，Treg细胞特异性TGF-β1缺陷小鼠肠系膜淋巴结中Treg细胞的频率显着降低，这与Treg细胞中IFN-γ产生者的频率增加有关。在树突状细胞介导的体外刺激以及体内过继转移研究中，TGF-β1缺陷的Treg细胞比TGF-β1充足的Treg细胞更容易表达IFN-γ。从机制上讲，TGF-β1缺陷的Treg细胞比TGF-β1充足的Treg细胞表达更高水平的Il12rb2 ，并且对IL-12诱导的转化为产生IFN-γ的Treg细胞或产生IFN-γ的exTreg细胞更敏感。我们的研究结果表明，自分泌 TGF-β1 通过下调 Treg 细胞上的 IL-12R，在 Treg 细胞的最佳抑制活性和稳定性中发挥着关键作用。