Immunology Section, Lund University, Lund 221 84, Sweden.
Immunity. 2013 May 23;38(5):958-69. doi: 10.1016/j.immuni.2013.03.009. Epub 2013 May 9.
CD103(+)CD11b(+) dendritic cells (DCs) represent the major migratory DC population within the small intestinal lamina propria (SI-LP), but their in vivo function remains unclear. Here we demonstrate that intestinal CD103(+)CD11b(+) DC survival was dependent on interferon regulatory factor 4 (IRF4). Mice with a DC deletion in Irf4 displayed reduced numbers of intestinal interleukin 17 (IL-17)-secreting helper T 17 (Th17) cells and failed to support Th17 cell differentiation in draining mesenteric lymph nodes (MLN) following immunization. The latter was associated with a selective reduction in CD103(+)CD11b(+) MLN DCs and DC derived IL-6. Immunized Il6(-/-) mice failed to support Th17 cell differentiation in MLN in vivo and CD103(+)CD11b(+) MLN DCs supported IL-6-dependent Th17 cell differentiation in vitro. Together, our results suggest a central role for IRF4-dependent, IL-6 producing CD103(+)CD11b(+) DCs in intestinal Th17 cell differentiation.
CD103(+)CD11b(+) 树突状细胞 (DCs) 代表了小肠固有层 (SI-LP) 中主要的迁移性 DC 群体，但它们的体内功能尚不清楚。在这里，我们证明了肠道 CD103(+)CD11b(+) DC 的存活依赖于干扰素调节因子 4 (IRF4)。在 Irf4 缺失的情况下，肠道产生白细胞介素 17 (IL-17) 的辅助性 T 细胞 17 (Th17) 细胞数量减少，并且在免疫后无法支持引流肠系膜淋巴结 (MLN) 中的 Th17 细胞分化。后者与 MLN 中 CD103(+)CD11b(+) DC 和 DC 衍生的 IL-6 的选择性减少有关。在体内，免疫的 Il6(-/-) 小鼠无法支持 MLN 中的 Th17 细胞分化，而 CD103(+)CD11b(+) MLN DC 则支持 IL-6 依赖性 Th17 细胞分化。总之，我们的结果表明，IRF4 依赖性、产生 IL-6 的 CD103(+)CD11b(+) DC 在肠道 Th17 细胞分化中起核心作用。
