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

C. C. Bain, J. Montgomery, C L Scott, J M Kel, M J H Girard-Madoux, L Martens, T F P Zangerle-Murray, J Ober-Blobaum, D Lindenbergh-Kortleve, J N Samsom, S. Henri, T Lawrence, Y Saeys, B. Malissen, M. Dalod, B E Clausen, Alan McI. Mowat

Research output: Contribution to journalArticlepeer-review

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 CD103CD11b+ 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 CD103CD11b+ 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.
Original languageEnglish
Article number620
Number of pages12
JournalNature Communications
Volume8
DOIs
Publication statusPublished - 20 Sep 2017

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