Lymphoid Tissue Development Unit - CNRS URA 1961
Aim
Adaptive immune responses are initiated in large and highly organized clusters of lymphocytes and antigen presenting cells, the lymph nodes and Peyer’s patches. Their development is programmed and initiated in the sterile environment of the fetus. A cascade of events is triggered by lymphoid tissue inducer (LTi) cells, which recapitulates the inflammatory reaction and culminates in the formation of complex structures carrying both specialized hematopoietic and stromal cells. In the recent years, we have shown that LTi cells belong to a large family of innate lymphoid cells (ILCs) that play critical roles in intestinal homeostasis, as well as early in immune responses to infection and injury. We have suggested that ILCs are the innate counterparts of T helper cells and regulate adaptive immunity. Furthermore, the symbiotic microbiota that colonizes the intestine after birth modulates the activity of ILCs and induces the formation of new intestinal lymphoid tissues through the activation of LTi cells. Thus, we aim at deciphering the constructive dialogue that develops between the microbiota and the immune system and leads to the formation of a mature and reactive network of cells and molecules required for homeostasis and defense. However, the mobile cells of the immune system remain blind without the guidance provided by stromal cells and their expression of cytokines and chemokines. We aim at identifying the stromal cells that are involved in the development and organization of immunity during ontogeny and immune responses. Altogether, we propose that the lymphocyte-stroma-microbiota trilogy is the functional unit that determines the reactivity of the host to infection and injury, and maintains homeostasis. Perturbation of this trilogy leads to inflammation and pathology, the mechanisms of which we aim at understanding to develop new avenues for prevention and therapy.