IRF8 Transcription-Factor-Dependent Classical Dendritic Cells Are Essential for Intestinal T Cell Homeostasis

Katarzyna M. Luda, Thorsten Joeris, Emma K. Persson, Aymeric Marie Christian Rivollier, Mimoza Demiri, Katarzyna Maria Sitnik, Lieneke Pool, Jacob B. Holm, F. Melo-Gonzalez, Lisa Richter, Bart N. Lambrecht, Karsten Kristiansen, Mark A. Travis, Marcus Svensson-Frej, Knut Kotarsky, William Winston Agace

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    Abstract

    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 CD8αβ+ and CD4+CD8αα+ T cells; the latter requiring β8 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.
    Original languageEnglish
    JournalImmunity
    Volume44
    Issue number4
    Pages (from-to)860-874
    Number of pages15
    ISSN1074-7613
    DOIs
    Publication statusPublished - 2016

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