Conventional CD4+ T cells regulate IL-22-producing intestinal innate lymphoid cells.
Conventional CD4+ T cells regulate IL-22-producing intestinal innate lymphoid cells.
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肠道内的先天免疫系统和适应性免疫系统相互配合，以维持肠道屏障的完整性，并调节常驻微生物群的组成。然而，我们对先天免疫系统和适应性免疫系统之间的相互作用知之甚少。我们发现CD4+ T细胞调节屏障保护性先天淋巴样细胞（ILCs）的数量和功能，以及抗菌肽（amp）、Reg3γ和Reg3β的产生。缺乏T细胞和B细胞的RAG1−/−小鼠的ILC数量、IL-22的产生和AMP的表达升高，通过替换CD4+ T细胞来纠正。缺乏CD4+ T细胞的MHCII−/−小鼠也增加了ILCs、IL-22和amp，表明CD4+ T细胞的负调控是在稳态下发生的。我们利用转移和转基因小鼠来证明IL-22的减少是由常规CD4+ T细胞介导的，并且依赖于tcr。IL-22-AMP轴响应共生菌；然而，在MHCII+/−和MHCII - /−的窝伴之间，细菌种类和共生细菌的总定位都没有差异。这些数据定义了CD4+ T细胞调节肠道产生il -22的ILCs和amp的新能力。
The innate and adaptive immune systems in the intestine cooperate to maintain the integrity of the intestinal barrier and to regulate the composition of the resident microbiota. However, little is known about the crosstalk between the innate and adaptive immune systems that contribute to this homeostasis. We find that CD4+ T cells regulate the number and function of barrier-protective innate lymphoid cells (ILCs), as well as, production of antimicrobial peptides (AMPs), Reg3γ and Reg3β. RAG1−/− mice lacking T and B cells had elevated ILC numbers, IL-22 production, and AMP expression which were corrected by replacement of CD4+ T cells. MHCII−/− mice lacking CD4+ T cells also had increased ILCs, IL-22, and AMPs, suggesting that negative regulation by CD4+ T cells occurs at steady state. We utilized transfers and genetically modified mice to show that reduction of IL-22 is mediated by conventional CD4+ T cells and is TCR-dependent. The IL-22-AMP axis responds to commensal bacteria; however, neither the bacterial repertoire nor the gross localization of commensal bacteria differed between MHCII+/− and MHCII−/− littermates. These data define a novel ability of CD4+ T cells to regulate intestinal IL-22-producing ILCs and AMPs.