Liens transverses ENS de Lyon

Agenda de l'ENS de Lyon

L’intégrine αvβ8, gardienne du TGFβ: implications de la régulation de son expression pour le contrôle dynamique des réponses immunitaires.

Date
jeu 07 fév 2019
Horaires

14h00

Lieu(x)

Amphithéâtre Pasteur - Tour CERVI - CIRI - 21 avenue Tony Garnier, 69007 Lyon

Intervenant(s)

Soutenance d'HDR de Mme Héléna PAÏDASSI sous la direction de M. Thierry DEFRANCE

Langue(s) des interventions

Description générale

Our immune system is commonly viewed as the army able to protect the organism from challenges to homeostasis: infection, tissue stress, injury, tumorigenesis. It is indeed remarkably potent in eliminating a threat but can also cause severe detrimental tissue damage if kept unchecked. How the immune system remains generally disengaged, while still keeping the ability to respond when necessary has always been a fascinating question to me. Throughout my career as an immunologist, I have been involved in several projects each tackling different aspects of the mechanisms of regulation of the immune response:

  1. Apoptotic cell recognition and immune tolerance

During my PhD, I established how the complement component C1q can bind to “eat me” signals exposed at the apoptotic cell surface for recognition by phagocytes, a key process to prevent the development of inflammation and autoimmunity. Recognition of dying cells not only allows the safe removal of apoptotic cells, but also promotes immune tolerance through the reprogramming of phagocytes. More recently, we identified a transcription factor involved in the immunosuppression of dendritic cells (DCs) and macrophage upon apoptotic cell uptake. We are now working at identifying the epigenetic mechanisms involved and analyze their role in sepsis-induced immunosuppression.

  1. Specialization of dendritic cells for orchestration of mucosal immune responses

Regulation of immune responses is a fascinating question, which takes on its full meaning in mucosae. In my postdoctoral work, I showed that αvβ8 integrin, which is required for TGFβ activation confers on intestinal DCs their specialized ability to induce TGFβ-dependent T cell responses. Upon my recruitment at CIRI, together with my group, we identified the factors regulating αvβ8 expression in DCs and established this process as a critical control point for orchestration of intestinal T cell responses. Importantly, TGFβ is also a critical regulator of mucosal B cell responses and is required to promote IgA class-switch in the gut. Therefore, we are now investigating the role of αvβ8-mediatied activation of TGFβ by DCs for the regulation of IgA class-switch in the gut, in particular in the context of viral infection.

  1. Regulation of B cell responses

The role of TGFβ in regulating humoral immune responses is not restricted to IgA class-switch. Based on promising preliminary results, my projects now aim at defining the contribution of αvβ8-mediated activation of TGFβ to antibody-mediated host defense and diseases, and to identify ways to control B cell responses by targeting αvβ8 expression.

Gratuit
Mots clés
Disciplines