Immunity
Volume 34, Issue 1, 28 January 2011, Pages 122-134
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Article
CD4+ Lymphoid Tissue-Inducer Cells Promote Innate Immunity in the Gut

https://doi.org/10.1016/j.immuni.2010.12.009Get rights and content
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Summary

Fetal CD4+ lymphoid tissue inducer (LTi) cells play a critical role in the development of lymphoid tissues. Recent studies identified that LTi cells persist in adults and are related to a heterogeneous population of innate lymphoid cells that have been implicated in inflammatory responses. However, whether LTi cells contribute to protective immunity remains poorly defined. We demonstrate that after infection with Citrobacter rodentium, CD4+ LTi cells were a dominant source of interleukin-22 (IL-22) early during infection. Infection-induced CD4+ LTi cell responses were IL-23 dependent, and ablation of IL-23 impaired innate immunity. Further, depletion of CD4+ LTi cells abrogated infection-induced expression of IL-22 and antimicrobial peptides, resulting in exacerbated host mortality. LTi cells were also found to be essential for host protective immunity in lymphocyte-replete hosts. Collectively these data demonstrate that adult CD4+ LTi cells are a critical source of IL-22 and identify a previously unrecognized function for CD4+ LTi cells in promoting innate immunity in the intestine.

Highlights

► CD4+ LTi cells are a critical source of IL-22 after enteric bacterial infection ► Infection-induced CD4+ LTi cell responses and innate immunity are dependent on IL-23 ► Depletion of CD4+ LTi cells abrogates innate immunity to enteric bacterial infection ► CD4+ LTi cells promote innate immunity in lymphopenic and lymphocyte-replete hosts.

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