Microbiome and immunosenescence of  T cells repertoire

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The intestinal microbiota is a major contributor of antigens recognized by intestinal CD4 T cells. How these antigens influence CD4 T cells immunosenescence and their effector functions in old mice and humans remains unclear. Therefore, there is a need to develop a standardized microbial flora that has a manageable size and resembles natural microbiome that when administered to old, frail individuals will rebalance their intestinal homeostasis. The goal of this proposal is to test if this new oligoclonal collection of mouse intestinal commensals (oligo-MM), designed by system and genome-based approaches to recapitulate complete microbiome can help revitalize an aging immune system. In particular, we will investigate how oligo-MM microbiota and its main component Akkermasia municiphila interacts with Cd4 T cells and discover immune epitopes that these cells recognize from this bacteria. In Aim 1 we will investigate how specific intestinal commensals influence activation and repertoire of CD4 T cells in old mice. In our Aim 2 we will demonstrate that A. municiphila derived antigens induce naïve CD4Foxp3- T cells conversion to CD4Foxp3+ pTregs and substantially increase the number of these cells in old mice. We hypothesize that the therapeutic administration of A. municiphila to old mice can improve tolerance to intestinal microbiota and reduce immunosenescence. Overall this research will help develop new strategies based on strictly controlled microbiota-based therapies to control intestinal inflammation in elderly.