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

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.