Objective "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." Fields of science natural sciencesbiological sciencesmicrobiologybacteriologymedical and health sciencesbasic medicinepathologymedical and health sciencesbasic medicinephysiologyhomeostasis Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) FP7-PEOPLE-2011-IEF - Marie-Curie Action: "Intra-European fellowships for career development" Call for proposal FP7-PEOPLE-2011-IEF See other projects for this call Funding Scheme MC-IEF - Intra-European Fellowships (IEF) Coordinator INSTITUT PASTEUR Address Rue du docteur roux 25-28 75724 Paris France See on map Region Ile-de-France Ile-de-France Paris Activity type Research Organisations Administrative Contact Marie-Laure Rosso (Dr.) Links Contact the organisation Opens in new window Website Opens in new window EU contribution No data
