TGFβR signalling controls CD103+CD11b+ dendritic cell development in the intestine

Bain, C.C. et al. (2017) TGFβR signalling controls CD103+CD11b+ dendritic cell development in the intestine. Nature Communications, 8, 620. (doi: 10.1038/s41467-017-00658-6) (PMID:28931816) (PMCID:PMC5607002)

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Abstract

CD103+CD11b+ dendritic cells (DCs) are unique to the intestine, but the factors governing their differentiation are unclear. Here we show that transforming growth factor receptor 1 (TGFβR1) has an indispensable, cell intrinsic role in the development of these cells. Deletion of Tgfbr1 results in markedly fewer intestinal CD103+CD11b+ DCs and a reciprocal increase in the CD103−CD11b+ dendritic cell subset. Transcriptional profiling identifies markers that define the CD103+CD11b+ DC lineage, including CD101, TREM1 and Siglec-F, and shows that the absence of CD103+CD11b+ DCs in CD11c-Cre.Tgfbr1fl/fl mice reflects defective differentiation from CD103−CD11b+ intermediaries, rather than an isolated loss of CD103 expression. The defect in CD103+CD11b+ DCs is accompanied by reduced generation of antigen-specific, inducible FoxP3+ regulatory T cells in vitro and in vivo, and by reduced numbers of endogenous Th17 cells in the intestinal mucosa. Thus, TGFβR1-mediated signalling may explain the tissue-specific development of these unique DCs.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Mowat, Professor Allan and Montgomery, Dr Jennifer and Bain, Mr Calum
Authors: Bain, C.C., Montgomery, J., Scott, C., Kel, J.M., Girard-Madoux, M.J.H., Martens, L., Zangerle-Murray, T.F.P., Ober-Blöbaum, J., Lindenbergh-Kortleve, D., Sansom, J.N., Henri, S., Lawrence, T., Saeys, Y., Malissen, B., Dalod, M., Clausen, B.E., and Mowat, A. M.
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: 620
Publisher Policy:Reproduced under a Creative Commons license

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
522461Resident and Inflammatory Macrophages in the IntestineAllan MowatWellcome Trust (WELLCOTR)094763/Z/10/ZIII -IMMUNOLOGY
526841Molecular Functions in DiseaseDarren MoncktonWellcome Trust (WELLCOTR)089892/Z/09/ZRI MOLECULAR CELL & SYSTEMS BIOLOGY
590501Wellcome 096988/Z - T Zangerle MurrayAllan MowatWellcome Trust (WELLCOTR)096988/Z/11/ZIII -IMMUNOLOGY