TGF beta R signalling controls CD103(+)CD11b(+) dendritic cell development in the intestine

C. C. Bain (1) , J. Montgomery (2) , C. L. Scott (2) , J. M. Kel (3) , M. J. H. Girard-Madoux (3) , L. Martens (4) , T. F. P. Zangerle-Murray (2) , J. Ober-Blobaum (3) , D. Lindenbergh-Kortleve (3) , J. N. Samsom (5) , S. Henri (2) , T. Lawrence (3) , Y. Saeys , Bernard Malissen (2) , M. Dalod (2) , B. E. Clausen , A. Mcl. Mowat

1 University of Glasgow
2 CIML - Centre d'Immunologie de Marseille - Luminy
3 Erasmus MC - Erasmus University Medical Center [Rotterdam]
4 UGENT - Universiteit Gent = Ghent University
5 Department of Applied Mathematics and Computer Science [Ghent]

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 (TGF beta beta R1) 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, TGF beta R1-mediated signalling may explain the tissue-specific development of these unique DCs.

Domaines: Immunologie

C. C. Bain, J. Montgomery, C. L. Scott, J. M. Kel, M. J. H. Girard-Madoux, et al.. TGF beta R signalling controls CD103(+)CD11b(+) dendritic cell development in the intestine. Nature Communications, 2017, 8 (1), ⟨10.1038/s41467-017-00658-6⟩. ⟨hal-01764675⟩