1. TGFβR signalling determines CD103+CD11b+ dendritic cell development in the intestine
- Author
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Bain, C. C., Montgomery, J., Scott, C L, Kel, J M, Girard-Madoux, M J H, Martens, L, Zangerle-Murray, T F P, Ober-Blobaum, J, Lindenbergh-Kortleve, D, Samsom, J N, Henri, S., Lawrence, T, Saeys, Y, Malissen, B., Dalod, M., Clausen, B E, and Mowat, Alan McI.
- Subjects
TheoryofComputation_ANALYSISOFALGORITHMSANDPROBLEMCOMPLEXITY ,chemical and pharmacologic phenomena ,hemic and immune systems - 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.
- Published
- 2017