TY - JOUR
T1 - TGFβR signalling determines CD103+CD11b+ dendritic cell development in the intestine
AU - Bain, C. C.
AU - Montgomery, J.
AU - Scott, C L
AU - Kel, J M
AU - Girard-Madoux, M J H
AU - Martens, L
AU - Zangerle-Murray, T F P
AU - Ober-Blobaum, J
AU - Lindenbergh-Kortleve, D
AU - Samsom, J N
AU - Henri, S.
AU - Lawrence, T
AU - Saeys, Y
AU - Malissen, B.
AU - Dalod, M.
AU - Clausen, B E
AU - Mowat, Alan McI.
PY - 2017/9/20
Y1 - 2017/9/20
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-017-00658-6
DO - 10.1038/s41467-017-00658-6
M3 - Article
SN - 2041-1723
VL - 8
JO - Nature Communications
JF - Nature Communications
M1 - 620
ER -