Foxo transcription factors control regulatory T cell development and function.
Foxo transcription factors control regulatory T cell development and function.
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DOI：
10.1016/j.immuni.2010.12.002
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发表时间：
2010-12-14
期刊：
影响因子：
32.4
通讯作者：
Hedrick SM
中科院分区：
文献类型：
--
作者：
Kerdiles YM;Stone EL;Beisner DR;McGargill MA;Ch'en IL;Stockmann C;Katayama CD;Hedrick SM
Foxo转录因子整合外在信号以调节细胞分裂、分化和存活，以及淋巴细胞和髓细胞的特定功能。在此我们发现，Foxo1的缺失严重阻碍了Foxp3 + 调节性T（Treg）细胞的发育，并且发育出来的细胞在体内无功能。功能缺失包括CTLA - 4受体表达减少，因为Ctla4基因是Foxo1的直接靶标。T细胞中Foxo1的特异性缺失导致了外分泌性胰腺炎、后肢瘫痪、多器官淋巴细胞浸润、抗核抗体产生以及生发中心扩大。在缺乏Foxo1的情况下，TGF - β细胞因子无法抑制T - bet转录因子，导致IFN - γ分泌，这进一步揭示了Foxo介导的对Treg细胞特性的调控。此外，Foxo3的缺失加剧了Foxo1缺失的影响。因此，Foxo转录因子引导T细胞分化的偶发事件以及效应细胞群的特定功能。
Foxo transcription factors integrate extrinsic signals to regulate cell division, differentiation and survival, and specific functions of lymphoid and myeloid cells. Here we showed the absence of Foxo1 severely curtailed the development of Foxp3+ regulatory T (Treg) cells, and those that developed were nonfunctional in vivo. The loss of function included diminished CTLA-4 receptor expression as the Ctla4 gene was a direct target of Foxo1. T cell specific loss of Foxo1 resulted in exocrine pancreatitis, hind limb paralysis, multi-organ lymphocyte infiltration, anti-nuclear antibodies and expanded germinal centers. Foxo-mediated control over Treg cell specification was further revealed by the inability of TGF-β cytokine to suppress T-bet transcription factor in the absence of Foxo1, resulting in IFN-γ-secretion. In addition the absence of Foxo3 exacerbated the effects of the loss of Foxo1. Thus, Foxo transcription factors guide the contingencies of T cell differentiation and specific functions of effector cell populations.
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