TGFβR signalling controls CD103+CD11b+ dendritic cell development in the intestine
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.
|Persistent URL||dx.doi.org/10.1038/s41467-017-00658-6, hdl.handle.net/1765/102064|
Bain, L.J, Montgomery, J. (J.), Scott, C.L, Kel, J.M, Girard-Madoux, M.J.H, Martens, L, … Mowat, A.M. (A. McI.). (2017). TGFβR signalling controls CD103+CD11b+ dendritic cell development in the intestine. Nature Communications, 8(1). doi:10.1038/s41467-017-00658-6