IRF8 Transcription-Factor-Dependent Classical Dendritic Cells Are Essential for Intestinal T Cell Homeostasis
IRF8 Transcription-Factor-Dependent Classical Dendritic Cells Are Essential for Intestinal T Cell Homeostasis
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DOI：
10.1016/j.immuni.2016.02.008
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发表时间：
2016-04-19
期刊：
影响因子：
32.4
通讯作者：
Agace, William W.
中科院分区：
文献类型：
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作者：
Luda, Katarzyna M.;Joeris, Thorsten;Agace, William W.
树突状细胞(DC)在肠道免疫动态平衡中的作用尚不完全清楚。在这里，我们显示缺乏IRF8转录因子依赖的DC的小鼠的小肠(SI)中的T细胞数量减少，但大肠(LI)中的T细胞数量没有减少，包括几乎完全缺乏SI CD8α(+)和CD4(+)CD8α(+)T细胞；后者需要迁移的IRF8依赖的CD103(+)CD11b(-)DC表达β8整合素。在肠系膜淋巴结(MLN)T细胞启动过程中，SI归巢受体的诱导受到抑制，这与SI来源的MLN树突状细胞的乙醛脱氢酶活性降低以及T细胞对SI的低效定位有关。这些小鼠也缺乏肠道T辅助1(Th1)细胞，无法支持MLN中Th1细胞的分化，也无法启动Th1细胞对旋毛虫感染的反应。总的来说，这些结果强调了依赖IRF8的DC在维持肠道T细胞稳态中的多个非冗余角色。
The role of dendritic cells (DCs) in intestinal immune homeostasis remains incompletely defined. Here we show that mice lacking IRF8 transcription-factor-dependent DCs had reduced numbers of T cells in the small intestine (SI), but not large intestine (LI), including an almost complete absence of SI CD8 alpha beta(+) and CD4(+)CD8 alpha alpha(+) T cells; the latter requiring beta 8 integrin expression by migratory IRF8 dependent CD103(+)CD11b(-) DCs. SI homing receptor induction was impaired during T cell priming in mesenteric lymph nodes (MLN), which correlated with a reduction in aldehyde dehydrogenase activity by SI-derived MLN DCs, and inefficient T cell localization to the SI. These mice also lacked intestinal T helper 1 (Th1) cells, and failed to support Th1 cell differentiation in MLN and mount Th1 cell responses to Trichuris muris infection. Collectively these results highlight multiple non-redundant roles for IRF8 dependent DCs in the maintenance of intestinal T cell homeostasis.