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Immunity. 2016 Apr 19;44(4):860-74. doi: 10.1016/j.immuni.2016.02.008. Epub 2016 Apr 5.

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

Author information

1
Immunology Section, Lund University, Lund 221 84, Sweden.
2
Section for Immunology and Vaccinology, National Veterinary Institute, Technical University of Denmark, 1870 Frederiksberg C, Denmark.
3
Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, 2100 Copenhagen, Denmark.
4
Manchester Collaborative Centre of Inflammation Research (MCCIR), University of Manchester, Manchester M13 9NT, UK; Wellcome Trust Centre for Cell-Matrix Research, University of Manchester, Manchester M13 9PT, UK; Manchester Immunology Group, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
5
Centre for Immune Regulation and Department of Pathology, Oslo University Hospital - Rikshospitalet and University of Oslo, 0027 Oslo, Norway.
6
Inflammation Research Center (IRC), VIB-UGent Department, 9052 Ghent, Belgium.
7
Immunology Section, Lund University, Lund 221 84, Sweden; Section for Immunology and Vaccinology, National Veterinary Institute, Technical University of Denmark, 1870 Frederiksberg C, Denmark. Electronic address: william.agace@med.lu.se.

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.

PMID:
27067057
DOI:
10.1016/j.immuni.2016.02.008
[Indexed for MEDLINE]
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