In green, cells called “lymphoid tissue inducers” which induce a local inflammation ; in red inflamed stromal cells; in blue macrophages. This process recapitulates inflammation after an infection or a wound in the sterile environment of the fetus, and leads to the recruitment of B and T cells, and to the construction of a lymph node.
A developing lymph node in a mouse fetus
Gérard Eberl is investigating immunity mecanisms. Pro-inflammatory cells, stromal cells and microbiota all interact to define health and immunity of the host, and its interaction with the environment. Using mouse models, Gérard Eberl and his team aim at defining the mechanisms by which these equilibria are maintained during health and broken during pathology.
Pro-inflammatory cells expressing the nuclear hormone receptor RORgt play a fundamental role in mucosal and skin defense, 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.
Realizations / Impact
Gérard Eberl and his team develop mouse models to understand how RORgt+ cells control mucosal and skin immunity, and how they respond to and shape microbiota. More generally, they aim at deciphering the mechanisms of the dialogue between microbiota and pro-inflammatory cells, a dialogue that affects host homeostasis and development of inflammatory pathologies.
An important partner in this dialogue is the stromal microenvironment, including vessels, perivascular cells and fibroblasts, which have essential roles in lymphocytes recruitment and survival through expression of adhesion molecules, chemokines and cytokines. When inappropriately activated by injury, specific subsets of stromal cells, such as ADAM12+ perivascular cells, contribute to pathogenesis by exacerbating inflammation and fibrosis. Stromal cells play therefore fundamental roles in homeostasis, inflammation and pathology.
Gérard Eberl proposes 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. As perturbation of this trilogy generates inflammation and pathology, he and his team aim at defining the underlying crosstalk and mechanisms in order to develop new avenues for prevention and therapy.
• 1996 : Ph.D. in Immunology , University of Lausanne, Switzerland, Giampetro Corradin's lab
• 1996-2000 : Postdoctoral fellow, Ludwig Institute for Cancer Research, Switzerland, H. Robson MacDonald's lab
• 2000-2003 : Postdoctoral fellow, Immunology Skirball Institute, New York, USA, Dan Littman's lab
• 2003 - 2004 : Visiting scientist, HIV and Malaria Vaccine Program, Aaron Diamond AIDS Research Center, Rockefeller University, New York
• 2005 : appointed head of the Lymphoid Tissue Development lab, Pasteur Institute, Paris, France
• EElected EMBO member, 2013
• Jacques Oudin Award, French Society of Immunology, 2013
• Pasteur Vallery-Radot Award, from the French National Library, 2012
• Georges Zermati Award, from the Fondation de France, 2011
• Grant from the Simone e Cino del Duca Foundation, Institut de France, 2010
Oct 2010, Science
Sep 2010, Mucosal Immunology