Different populations of CD11b+ dendritic cells drive Th2 responses in the small intestine and colon

Mayer, J. U., Demiri, M., Agace, W. W., MacDonald, A. S., Svensson-Frej, M. and Milling, S. W. (2017) Different populations of CD11b+ dendritic cells drive Th2 responses in the small intestine and colon. Nature Communications, 8, 15820. (doi: 10.1038/ncomms15820) (PMID:28598427) (PMCID:PMC5472728)

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Abstract

T-helper 2 (Th2) cell responses defend against parasites. Although dendritic cells (DCs) are vital for the induction of T-cell responses, the DC subpopulations that induce Th2 cells in the intestine are unidentified. Here we show that intestinal Th2 responses against Trichuris muris worms and Schistosoma mansoni eggs do not develop in mice with IRF-4-deficient DCs (IRF-4f/f CD11c-cre). Adoptive transfer of conventional DCs, in particular CD11b-expressing DCs from the intestine, is sufficient to prime S. mansoni-specific Th2 responses. Surprisingly, transferred IRF-4-deficient DCs also effectively prime S. mansoni-specific Th2 responses. Egg antigens do not induce the expression of IRF-4-related genes. Instead, IRF-4f/f CD11c-cre mice have fewer CD11b+ migrating DCs and fewer DCs carrying parasite antigens to the lymph nodes. Furthermore, CD11b+CD103+ DCs induce Th2 responses in the small intestine, whereas CD11b+CD103− DCs perform this role in the colon, revealing a specific functional heterogeneity among intestinal DCs in inducing Th2 responses.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Milling, Professor Simon and Mayer, Mr Johannes
Authors: Mayer, J. U., Demiri, M., Agace, W. W., MacDonald, A. S., Svensson-Frej, M., and Milling, S. W.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Nature Communications
Publisher:Nature Publishing Group
ISSN:2041-1723
ISSN (Online):2041-1723
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Nature Communications 8:15820
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
615931Molecular Functions in Disease (Phd Studentship 2012-2016)Simon MillingWellcome Trust (WELLCOTR)099784/Z/12/ZIII -IMMUNOLOGY
618121The Functions of Migrating Intestinal Dendritic Cells in Tolerance and Immunity.Simon MillingMedical Research Council (MRC)MR/K021095/1III -IMMUNOLOGY