IFNγ signaling endows DCs with the capacity to control type I inflammation during parasitic infection through promoting T-bet+ regulatory T cells. Mus musculus

Transcriptome analysis of IFNγ-insensitive DCs IFNγ signaling drives dendritic cells (DCs) to promote type I T cell (Th1) immunity. Here, we show that activation of DCs by IFNγ is equally crucial for the differentiation of a population of T-bet+ regulatory T (Treg) cells specialized to inhibit Th1 immune responses. Conditional deletion of IFNγ receptor in DCs but not in Treg cells resulted in a severe defect in this specific Treg cell subset, leading to exacerbated immune pathology during parasitic infections. Mechanistically, IFNγ-unresponsive DCs failed to produce sufficient amount of IL-27, a cytokine required for optimal T-bet induction in Treg cells. Thus, IFNγ signalling endows DCs with the ability to efficiently control a specific type of T cell immunity through promoting a corresponding Treg cell population. Overall design: We analyzed 3 WT DC samples and 3 IFNγR2 KO DC samples isolated from unmanipulated mice. In addition, we analyzed 3 WT DC samples and 3 IFNγR2 KO DC samples isolated from mixed BM chimeras (WT + IFNgR2KO) day 8 T. gondii infected.

干扰素γ（IFNγ）不敏感型树突状细胞（DCs）的转录组分析
干扰素γ信号通路可驱动树突状细胞（DCs）介导I型T细胞（Th1）免疫应答。本研究发现，干扰素γ对树突状细胞的激活，同样是分化一类特异性抑制Th1免疫应答的T-bet阳性调节性T（Treg）细胞亚群的关键条件。仅在树突状细胞中条件性敲除干扰素γ受体（而非在调节性T细胞中），会导致该特异性Treg细胞亚群出现严重缺陷，进而在寄生虫感染过程中加剧免疫病理损伤。从机制层面分析，无法响应干扰素γ的树突状细胞无法分泌足量的白细胞介素27（IL-27）——该细胞因子是在调节性T细胞中最优诱导T-bet表达所必需的。综上，干扰素γ信号通路可赋予树突状细胞能力，通过促进对应Treg细胞亚群，实现对特定类型T细胞免疫的高效调控。
实验设计概述：本研究分析了3份来自未处理小鼠的野生型（WT）树突状细胞样本与3份同来源的干扰素γ受体2敲除（IFNγR2 KO）树突状细胞样本。此外，本研究还分析了3份来自混合骨髓嵌合体（WT + IFNγR2 KO）小鼠的野生型树突状细胞样本，以及3份同来源的干扰素γ受体2敲除树突状细胞样本，这些小鼠均在感染刚地弓形虫（T. gondii）第8天时取样。