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

调节性T （Treg）细胞介导胃肠道对食物和微生物群的耐受。我们最近提出了一个逐步口服耐受诱导模型，包括在肠道引流淋巴结中产生Treg，它们迁移到肠道，随后由常驻肠道巨噬细胞驱动Treg扩张。这个模型引导我们提出假设和关键问题，这些问题将在本研究计划中进行研究。我们主要研究：1)抗原转运和递呈机制；2)新生儿和成人淋巴细胞迁移对口服耐受诱导的功能影响；3)Treg从肠层的输出。我们期望这些实验将完善我们对肠道耐受性的理解，同时表征可以靶向调节肠道耐受性的机制和分子。

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.