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Nat Commun. 2017 Sep 20;8(1):620. doi: 10.1038/s41467-017-00658-6.

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

Author information

1
Centre for Immunobiology, Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary Medicine and Life Sciences, University of Glasgow, Glasgow, G12 8TJ, UK.
2
The University of Edinburgh/MRC Centre for Inflammation Research, University of Edinburgh, Edinburgh, EH16 4TJ, UK.
3
Laboratory of Myeloid Cell Ontogeny and Functional Specialization, VIB-UGent Center for Inflammation Research, Technologiepark, Ghent 927, Belgium.
4
Department of Biomedical Molecular Biology, Ghent University, Ghent, 9000, Belgium.
5
Department of Immunology, Erasmus MC, University Medical Center, 3015 GE, Rotterdam, The Netherlands.
6
Data Mining and Modeling for Biomedicine, VIB Inflammation Research Center, Ghent, 9052, Belgium.
7
Faculty of Biology, Medicine and Health and Manchester Collaborative Centre for Inflammation Research, University of Manchester, Manchester, M13 9PT, UK.
8
Institute for Molecular Medicine, University Medical Centre of the Johannes Gutenberg University, 55131, Mainz, Germany.
9
Laboratory of Pediatrics, Division of Gastroenterology and Nutrition, Erasmus Medical Center, Rotterdam, 3015 GE, The Netherlands.
10
Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, INSERM, U1104, CNRS UMR7280, 13288, Marseille, France.
11
Department of Applied Mathematics, Computer Science and Statistics, Ghent University, Ghent, 9000, Belgium.
12
Department of Immunology, Erasmus MC, University Medical Center, 3015 GE, Rotterdam, The Netherlands. bclausen@uni-mainz.de.
13
Institute for Molecular Medicine, University Medical Centre of the Johannes Gutenberg University, 55131, Mainz, Germany. bclausen@uni-mainz.de.
14
Centre for Immunobiology, Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary Medicine and Life Sciences, University of Glasgow, Glasgow, G12 8TJ, UK. allan.mowat@glasgow.ac.uk.

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.Tgfbr1 fl/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.Developmental cues for the different dendritic cell (DC) subsets in the intestine are yet to be defined. Here the authors show that TGFβR1 signalling is needed for development of CD103+CD11b+ intestinal DCs from CD103-CD11b+ cells and that they contribute to the generation of Th17 and regulatory T cells.

PMID:
28931816
PMCID:
PMC5607002
DOI:
10.1038/s41467-017-00658-6
[Indexed for MEDLINE]
Free PMC Article

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