Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), 138648 Singapore.
Immunity. 2013 May 23;38(5):970-83. doi: 10.1016/j.immuni.2013.04.011.
Mouse and human dendritic cells (DCs) are composed of functionally specialized subsets, but precise interspecies correlation is currently incomplete. Here, we showed that murine lung and gut lamina propria CD11b+ DC populations were comprised of two subsets: FLT3- and IRF4-dependent CD24(+)CD64(-) DCs and contaminating CSF-1R-dependent CD24(-)CD64(+) macrophages. Functionally, loss of CD24(+)CD11b(+) DCs abrogated CD4+ T cell-mediated interleukin-17 (IL-17) production in steady state and after Aspergillus fumigatus challenge. Human CD1c+ DCs, the equivalent of murine CD24(+)CD11b(+) DCs, also expressed IRF4, secreted IL-23, and promoted T helper 17 cell responses. Our data revealed heterogeneity in the mouse CD11b+ DC compartment and identifed mucosal tissues IRF4-expressing DCs specialized in instructing IL-17 responses in both mouse and human. The demonstration of mouse and human DC subsets specialized in driving IL-17 responses highlights the conservation of key immune functions across species and will facilitate the translation of mouse in vivo findings to advance DC-based clinical therapies.
小鼠和人类树突状细胞（DC）由功能特化的亚群组成，但目前种间相关性尚不完全清楚。在这里，我们表明，鼠肺和肠道固有层 CD11b+DC 群体由两个亚群组成：FLT3 和 IRF4 依赖性 CD24+CD64- DC 和污染的 CSF-1R 依赖性 CD24-CD64+巨噬细胞。功能上，缺失 CD24+CD11b+DC 会破坏稳定状态和烟曲霉攻击后 CD4+T 细胞介导的白细胞介素-17（IL-17）产生。人 CD1c+DC 是鼠 CD24+CD11b+DC 的等价物，也表达 IRF4，分泌 IL-23，并促进辅助性 T 细胞 17 型反应。我们的数据揭示了小鼠 CD11b+DC 隔室中的异质性，并鉴定了黏膜组织中表达 IRF4 的 DC，它们专门在鼠和人中指导 IL-17 反应。证明小鼠和人类 DC 亚群专门驱动 IL-17 反应突出了关键免疫功能在物种间的保守性，并将促进基于 DC 的临床治疗的小鼠体内发现的转化。
