T-bet is a STAT1-induced regulator of IL-12R expression in naive CD4+ T cells
T-bet is a STAT1-induced regulator of IL-12R expression in naive CD4+ T cells
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DOI：
10.1038/ni794
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发表时间：
2002-06-01
影响因子：
30.5
通讯作者：
Murphy, KM
中科院分区：
文献类型：
--
作者：
Afkarian, M;Sedy, JR;Murphy, KM
1型T辅助细胞（T（H）1）的发育涉及通过信号转导和转录激活因子1（STAT 1）的干扰素-γ（IFN-γ）信号传导和通过STAT 4激活的白细胞介素-12（IL-12）信号传导。我们在这里研究了T-bet调节，并评估了T-bet在STAT 1和STAT 4依赖性T（H）1发育过程中的作用。我们发现T细胞活化过程中T-bet的表达强烈依赖于IFN-γ信号传导和STAT 1活化，但不依赖于STAT 4。异位T-bet表达强烈地增加PMA-离子霉素激活的T（H）2细胞中IFN-γ的产生，但微弱地增加IL-12-IL-18或OVA肽-抗原呈递细胞刺激刺激的T（H）2细胞中IFN-γ的产生。相比之下，IL-12-IL-18诱导的IFN-γ产生尽管有异位T-bet表达，但仍保持STAT 4依赖性。在野生型和STAT 1（-/-）T（H）2细胞中，异位T-bet表达选择性诱导IL-12 R β 2的表达，但不诱导IL-18 R α的表达，但不消除加塔-3和T（H）2细胞因子的表达。最后，异位T-bet并不直接诱导内源性T-bet的表达，独立于IFN-γ或STAT 1。因此，T-bet在T细胞活化期间由IFN-γ和STAT 1信号传导诱导。此外，T-bet介导T（H）1发育的STAT 1依赖性过程，包括诱导IL-12 R β 2。
T helper type 1 (T(H)1) cell development involves interferon-gamma (IFN-gamma) signaling through signal transducer and activator of transcription 1 (STAT1) and interleukin-12 (IL-12) signaling through STAT4 activation. We examined here T-bet regulation and evaluated the actions of T-bet in STAT1- and STAT4-dependent T(H)1 development processes. We found that T-bet expression during T cell activation was strongly dependent on IFN-gamma signaling and STAT1 activation, but was independent of STAT4. Ectopic T-bet expression strongly increased IFN-gamma production in T(H)2 cells activated by PMA-ionomycin, but weakly increased IFN-gamma production in T(H)2 cells stimulated by IL-12-IL-18 or OVA peptide-antigen-presenting cell stimulation. In contrast, IL-12-IL-18-induced IFN-gamma production remained STAT4-dependent despite ectopic T-bet expression. Ectopic T-bet expression selectively induced expression of IL-12Rbeta2, but not IL-18Ralpha in wild-type and STAT1(-/-) T(H)2 cells, but did not extinguish expression of GATA-3 and T(H)2 cytokines. Finally, ectopic T-bet did not directly induce expression of endogenous T-bet independently of IFN-gamma or STAT1. Thus, T-bet is induced by IFN-gamma and STAT1 signaling during T cell activation. In addition, T-bet mediates STAT1- dependent processes of T(H)1 development, including the induction of IL-12Rbeta2.