Obiettivo
"The nuclear hormone receptor RORγt marks a family of pro-inflammatory lymphoid cells, which includes adaptive IL-17-producing helper T cells (Th17), as well as subsets of innate lymphoid cells (ILCs), such as lymphoid tissue inducer (LTi) cells and IL 22-producing NKp46+ cells. These cells are required for the development of lymphoid tissues, homeostasis with symbiotic microbiota and defense against pathogens. The development and activity of RORγt+ ILCs are programmed to pre-empt intestinal colonization by bacterial symbionts and in turn, symbionts regulate the activity of RORγt+ ILCs. Thus, an equilibrated crosstalk between RORγt+ ILCs, microbiota, pathogens and adaptive immunity develops that is critical for intestinal homeostasis, a loss of which leads to inflammatory immunopathology. This project aims at understanding which and how symbiotic microbes induce and regulate RORγt+ ILCs, and how these cells control microbiota during homeostasis. To that end, GF mice will be colonized with symbiotic bacteria shown to correlate with RORγt+ ILC number and activity in normal mice. The mechanisms of regulation will then be dissected in vivo in a panel of mutant or antibody treated mice as well as in in vitro experiments. This study also aims at understanding how the homeostatic crosstalk between symbionts and RORγt+ ILCs breaks down during inflammatory pathology. In mice that lack RORγt+ ILCs, the structure of the bacterial community and propensity to develop immunopathology will be determined. Conversely, it will be tested whether inflammatory immunopathology leads to a disequilibrium between microbiota and ILCs. A better understanding of the mechanisms leading to a loss of homeostasis and immunopathological reactions is necessary to the design of new and more effective preventive and therapeutic strategies against intestinal immunopathologies. The study will be carried out in the Lymphoid Tissue Development Unit at Institut Pasteur in Paris."
Campo scientifico
Argomento(i)
Invito a presentare proposte
FP7-PEOPLE-2011-IEF
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Meccanismo di finanziamento
MC-IEF - Intra-European Fellowships (IEF)Coordinatore
75724 Paris
Francia