Li Ming O, Wan Yisong Y, Flavell Richard A
Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Immunity. 2007 May;26(5):579-91. doi: 10.1016/j.immuni.2007.03.014. Epub 2007 May 3.
TGF-beta1 is a regulatory cytokine with a pleiotropic role in immune responses. TGF-beta1 is widely expressed in leukocytes and stromal cells. However, the functions of TGF-beta1 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-beta1 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-beta1 promoted Th17-cell differentiation and was indispensable for the induction of experimental autoimmune encephalomyelitis. These findings reveal essential roles for T cell-produced TGF-beta1 in controlling differentiation of T helper cells and controlling inflammatory diseases.
转化生长因子-β1（TGF-β1）是一种在免疫反应中具有多效性作用的调节性细胞因子。TGF-β1在白细胞和基质细胞中广泛表达。然而，特定细胞谱系表达的TGF-β1在体内的功能仍不清楚。在此，我们表明，Tgfb1基因T细胞特异性缺失的小鼠在多个器官中出现致命的免疫病理，这种情况与T细胞增殖、活化增强以及CD4⁺T细胞分化为辅助性T细胞1（Th1）和Th2细胞有关。在转移模型中，由表达Foxp3的调节性T细胞产生的TGF-β1是抑制Th1细胞分化和炎症性肠病所必需的。此外，T细胞产生的TGF-β1促进Th17细胞分化，并且对于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TGF-β1在控制辅助性T细胞分化和控制炎症性疾病中的重要作用。
