T cell-produced transforming growth factor-β1 controls T cell tolerance and regulates Th1- and Th17-cell differentiation
T cell-produced transforming growth factor-β1 controls T cell tolerance and regulates Th1- and Th17-cell differentiation
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DOI：
10.1016/j.immuni.2007.03.014
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发表时间：
2007-05-01
期刊：
影响因子：
32.4
通讯作者：
Flavell, Richard A.
中科院分区：
文献类型：
--
作者：
Li, Ming O.;Wan, Yisong Y.;Flavell, Richard A.
转化生长因子-β1是一种调节细胞因子，在免疫反应中具有多效性作用。转化生长因子-β1广泛表达于白细胞和基质细胞。然而，体内特定细胞系表达的转化生长因子-β1的功能仍不清楚。在这里，我们显示了T细胞特异性Tgfb1基因缺失的小鼠在多个器官中发生了致命性的免疫病理，这种发展与T细胞的增殖、激活和CD4(+)T细胞向辅助性T细胞1(Th1)和Th2细胞的分化增强有关。在转移模型中，表达Foxp3的调节性T细胞产生的转化生长因子-β1需要抑制Th1细胞的分化和炎症性肠病。此外，T细胞产生的转化生长因子-β1促进Th17细胞分化，对实验性自身免疫性脑脊髓炎的诱导是不可或缺的。这些发现揭示了T细胞产生的转化生长因子-β1在控制T辅助细胞的分化和控制炎症性疾病中的重要作用。
TGF-beta 1 is a regulatory cytokine with a pleiotropic role in immune responses. TGF-beta 1 is widely expressed in leukocytes and stromal cells. However, the functions of TGF-beta 1 expressed by specific lineages of cells remain unknown in vivo. Here, we show that mice with a T cell-specific deletion of the Tgfb1 gene developed lethal immunopathology in multiple organs, and this development was associated with enhanced T cell proliferation, activation, and CD4(+) T cell differentiation into T helper 1 (Th1) and Th2 cells. TGF-beta 1 produced by Foxp3-expressing regulatory T cells was required to inhibit Th1-cell differentiation and inflammatory-bowel disease in a transfer model. In addition, T cell-produced TGF-beta 1 promoted Th17-cell differentiation and was indispensable for the induction of experimental autoimmune encephalomyelitis. These findings reveal essential roles for T cell-produced TGF-beta 1 in controlling differentiation of T helper cells and controlling inflammatory diseases.