CCR2+CD103 intestinal dendritic cells develop from DC-committed precursors and induce interleukin-17 production by T cells

Scott, C.L. et al. (2014) CCR2+CD103 intestinal dendritic cells develop from DC-committed precursors and induce interleukin-17 production by T cells. Mucosal Immunology, 8(2), pp. 327-339. (doi: 10.1038/mi.2014.70)

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Publisher's URL: http://dx.doi.org/10.1038/mi.2014.70

Abstract

The identification of intestinal macrophages (mφs) and dendritic cells (DCs) is a matter of intense debate. Although CD103<sup>+</sup> mononuclear phagocytes (MPs) appear to be genuine DCs, the nature and origins of CD103<sup>−</sup> MPs remain controversial. We show here that intestinal CD103<sup>−</sup>CD11b<sup>+</sup> MPs can be separated clearly into DCs and mφs based on phenotype, gene profile, and kinetics. CD64<sup>−</sup>CD103<sup>−</sup>CD11b<sup>+</sup> MPs are classical DCs, being derived from Flt3 ligand-dependent, DC-committed precursors, not Ly6C<sup>hi</sup> monocytes. Surprisingly, a significant proportion of these CD103<sup>−</sup>CD11b<sup>+</sup> DCs express CCR2 and there is a selective decrease in CD103<sup>−</sup>CD11b<sup>+</sup> DCs in mice lacking this chemokine receptor. CCR2<sup>+</sup>CD103<sup>−</sup> DCs are present in both the murine and human intestine, drive interleukin (IL)-17a production by T cells <i>in vitro</i>, and show constitutive expression of IL-12/IL-23p40. These data highlight the heterogeneity of intestinal DCs and reveal a <i>bona fide</i> population of CCR2<sup>+</sup>DCs that is involved in priming mucosal T helper type 17 (Th17) responses.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Mowat, Professor Allan and Bain, Mr Calum and Milling, Professor Simon and Wright, Miss Pamela and Scott, Mrs Clarice
Authors: Scott, C.L., Bain, C.C., Wright, P.B., Sichien, D., Kotarsky, K., Persson, E.K., Luda, K., Guilliams, M., Lambrecht, B.N., Agace, W.W., Milling, S.W.F., and Mowat, A.M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Mucosal Immunology
Publisher:Nature Publishing Group
ISSN:1933-0219
ISSN (Online):1935-3456
Copyright Holders:Copyright © 2014 The Authors
First Published:First published in Mucosal Immunology
Publisher Policy:Reproduced under a Creative Commons License
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
526841Molecular Functions in DiseaseDarren MoncktonWellcome Trust (WELLCOME)089892/Z/09/ZRI MOLECULAR CELL & SYSTEMS BIOLOGY