Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06520, USA.
Immunity. 2013 Oct 17;39(4):722-32. doi: 10.1016/j.immuni.2013.08.028. Epub 2013 Sep 26.
CD4⁺ T cell differentiation is regulated by specialized antigen-presenting cells. Dendritic cells (DCs) produce cytokines that promote naive CD4⁺ T cell differentiation into T helper 1 (Th1), Th17, and inducible T regulatory (iTreg) cells. However, the initiation of Th2 cell responses remains poorly understood, although it is likely that more than one mechanism might be involved. Here we have defined a specific DC subset that is involved in Th2 cell differentiation in vivo in response to a protease allergen, as well as infection with Nippostrongylus brasiliensis. We have demonstrated that this subset is controlled by the transcription factor interferon regulatory factor 4 (IRF4), which is required for their differentiation and Th2 cell-inducing function. IRF4 is known to control Th2 cell differentiation and Th2 cell-associated suppressing function in Treg cells. Our finding suggests that IRF4 also plays a role in DCs where it controls the initiation of Th2 cell responses.
CD4⁺ T 细胞的分化受专门的抗原呈递细胞调控。树突状细胞（DCs）产生细胞因子，促进初始 CD4⁺ T 细胞分化为 T 辅助 1（Th1）、Th17 和诱导性 T 调节（iTreg）细胞。然而，Th2 细胞反应的启动仍知之甚少，尽管可能涉及不止一种机制。在这里，我们已经确定了一种特定的 DC 亚群，它参与了体内针对蛋白酶过敏原以及感染巴西旋毛虫的 Th2 细胞分化。我们已经证明，该亚群受转录因子干扰素调节因子 4（IRF4）的控制，这对于它们的分化和 Th2 细胞诱导功能是必需的。IRF4 已知控制 Th2 细胞分化和 Treg 细胞中的 Th2 细胞相关抑制功能。我们的发现表明，IRF4 也在 DC 中发挥作用，控制 Th2 细胞反应的启动。
