Mechanism of transforming growth factor beta-induced inhibition of T helper type 1 differentiation.
Mechanism of transforming growth factor beta-induced inhibition of T helper type 1 differentiation.
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DOI：
10.1084/jem.20012076
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发表时间：
2002-06-03
期刊：
影响因子：
--
通讯作者：
Flavell RA
中科院分区：
文献类型：
--
作者：
Gorelik L;Constant S;Flavell RA
Regulation by transforming growth factor (TGF)-β plays an important role in immune homeostasis. TGF-β inhibits T cell functions by blocking both proliferation and differentiation. Here we show that TGF-β blocks Th1 differentiation by inhibiting the expression of T-bet, the apparent masterregulator of T helper (Th)1 differentiation. Restoration of T-bet expression through retroviral transduction of T-bet into developing Th1 cells abrogated the inhibitory effect of TGF-β. In addition, we show that, contrary to prior suggestions, downregulation of interleukin 12 receptor β2 chain is not key to the TGF-β–mediated effect. Furthermore, we show that the direct inhibitory effect of TGF-β on T cells is responsible, at least in part, for the inability of BALB/c mice to mount a Leishmania-specific Th1 response and to clear Leishmanial infection.
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