Transcriptional profiling of small intestinal lamina propria Dendritic cells by microarray

CD103+CD11b+ dendritic cells (DC) are unique to the intestine, but the factors governing their differentiation are unclear. Here we show that transforming growth factor receptor 1 (TGF beta 1) 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 CD103CD11b+ DC 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 CD103CD11b+ 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 (Treg) cells in vitro and in vivo, and by reduced numbers of endogenous TH17 cells in the intestinal mucosa. Thus, TGF beta 1 mediated signalling may explain the tissue-specific development of these unique DCs.

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Bain CC, Montgomery J, Scott CL, Kel JM, Girard-Madoux MJH, Martens L, Zangerle-Murray TFP, Ober-Blöbaum J, Lindenbergh-Kortleve D, Samsom JN, Henri S, Lawrence T, Saeys Y, Malissen B, Dalod M, Clausen BE, Mowat AM