The impact of migratory routes on intestinal tolerance in neonatal and adult mice

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Regulatory T (Treg) cells mediate tolerance to food and microbiota in the gastrointestinal tract. We have recently proposed a model of stepwise oral tolerance induction comprising the generation of Treg in the gut draining lymph nodes, their migration into the gut and subsequently the expansion of Treg driven by resident intestinal macrophages. This model lead us to propose hypothesis and key questions which will be investigated in this research proposal. We concentrate on 1) mechanisms of antigen transport and presentation 2) functional consequences of lymphocyte migration in neonates and adults for oral tolerance induction 3) the egress of Treg from the intestinal lamina. We expect that these experiments will refine our understanding of intestinal tolerance and at the same time characterize mechanisms and molecules that can be targeted to modulate intestinal tolerance.