Lymphoid Tissue Development Unit
Pro-inflammatory cells expressing the nuclear hormone receptor RORgt play a fundamental role in mucosal and skin defence, as well as in the development of lymphoid tissues. RORgt+ cells are also involved in inflammatory pathologies, such as inflammatory bowel diseases and arthritis, and are the target of a new generation of anti-inflammatory drugs blocking RORgt. RORgt+ cells include innate lymphoid cells (ILCs) that are programmed to induce the development of lymphoid tissues and induce early mucosal and skin immunity against microbes, as well as subsets of T cells, such as Th17 cells that react to microbiota. We develop mouse models to understand how RORgt+ cells control mucosal and skin immunity, and how they respond to and shape microbiota. More generally, we aim to decipher the mechanisms of the dialogue between microbiota and pro-inflammatory cells, a dialogue that affects homeostasis of the host and the development of inflammatory pathologies. An important partner in this dialogue are stromal cells, such as epithelial cells that are in direct contact with microbiota, and fibroblasts that direct the movement of cells and promote their survival through the expression of chemokines and cytokines. Stromal cells play therefore fundamental roles in inflammation and pathology. We propose that the lymphocyte-stroma-microbiota trilogy is the functional unit that determines the reactivity of the host to infection, injury and cancer, and drives homeostasis. Perturbation of this trilogy generates inflammation and pathology, the mechanisms of which we aim to understand to develop new avenues for prevention and therapy.