The influence of stroma cells on the generation and function of FoxP3- expressing regulatory T cells in the intestinal immune system

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FoxP3-expressing regulatory T cells (Treg) are centrally involved in the immunoregulation and key to understanding intestinal tolerance to food antigens. In this grant proposal we will analyze the role of non-hematopoietic stroma cells for the differentiation and function of Treg in the intestinal immune system. Retinoic acid (RA) acts as a co-factor in the TGF-β mediated conversion of naïve T cells to Treg. Moreover, RA induces the chemokine receptor CCR9 and α4β7-integrin, which mediate the migration of T cells into the gut. We demonstrated that in vivo stroma cells in the mesenteric lymph nodes are critical for the instructive function of RA in the induction of gut homing molecules. In this proposal we investigate in vitro and in vivo the RA-dependent and RA-independent influences of stroma cells on the differentiation and function of Treg in vitro and in vivo. Moreover, we will investigate the mechanisms that shape the lymph node specific identity and function of stroma cells and include stroma cells of the intestinal lamina propria in our experiments. Preliminary experiments showed that in the lamina propria Treg show a higher rate of proliferation than in secondary lymphoid organs. Thus, we will test the hypothesis that lamina propria stroma cells shape a unique environment in the intestine which allows for the expansion of Treg, thereby contributing to intestinal tolerance.