RESEARCH PROJECT

LYMPHOCYTE HOMEOSTASIS AND AUTOIMMUNITY

Our team focuses on the basic mechanisms ensuring B- and T-cell homeostasis. We closely investigate tolerance breakdown leading to the development of autoimmunity during autoimmune diseases (in particular systemic lupus erythematosus (SLE), antiphospholipid syndrome, and systemic sclerosis) and during primary immunodeficiencies, using murine models (cell lines, transgenic mice) as well as human samples from patients. We also investigate the role of the autophagy machinery in these contexts. Our research is facilitated by our close collaboration with the Department of Clinical Immunology and Internal Medicine (Strasbourg University Hospital; Head: Pr. Anne-Sophie Korganow) and the French National reference center for systemic autoimmune diseases East South-West (RESO) (Head: Pr Thierry Martin).

Our team is composed of 7 permanent researchers (2 PU-PH-MD, 1 PU-PH-PharmD, 1 MCU-PH-MD, 1 MCU-PH-dental surgery, 1 MCU-PH-PharmD, and 1 MCU) from 4 different Faculties, 2 engineers and students.

Current projects (Models):

  • Genetic studies and functional genomics for a better comprehension of B cell tolerance breakdown in autoimmune situations (SLE, antiphospholipid syndrome – Primary Immunodeficiencies)
  • PERSONALIS: Personalized medicine platform for autoimmune diseases
  • Consequences of STING gain of function on the development and phenotype of lymphocytes (CrisprCas9 mouse model)
  • Role of ERN1 in lymphocyte homeostasis and autoimmunity (CrisprCas9 mouse model)
  • Functional validation of a new phosphatase involved in T cell signaling (CrisprCas9 human cell lines, proteomic analysis)
  • Role of autophagy-related proteins in BCR trafficking (autophagy-deficient mouse models)
  • Role of ATG proteins in Langerhans Cell Homeostasis (autophagy and LAP-deficient models)
  • Role of LC3-associated phagocytosis in the development of systemic sclerosis in humans

EXTERNAL COLLABORATIONS

Dr I. André (Imagine, France)

Dr F. Rieux-Laucat (Imagine, France)

Pr Y. Crow (Imagine, France)

Dr S. Chan & P. Kirstetter (IGMBC, France)

Pr H. Dollfus (U1112, France)

Dr V. Flacher (IBMC, France)

Dr N. Charlet (IGBMC, France)

Dr M. Rizzi (Freiburg, Germany)

Pr B. Grimbacher (Freiburg, Germany)

Dr M. Proietti (Freiburg, Germany)

Pr E. Meffre (Yale, USA)

Dr Markus Munschen (COH, USA)

Pr Enkelejda Miho (Basel, Switzerland)

Pr Sophie Janssens (Ghent, Belgium)

Dr Bertrand Boisson (Rockfeller, USA)

Pr Christian Münz (Zürich-Switzerland)

FUNDINGS

  • Agence Nationale de la Recherche (ANR)
  • Interreg & Offensive Sciences
  • Idex (University of Strasbourg)
  • Fondation pour la Recherche Médicale (FRM)
  • Arthritis Foundation
  • SATT Connectus
  • Centre de référence des déficits immunitaires héréditaires (CEREDIH)
  • Groupe Français de Recherche sur la sclérodermie (GFRS)
  • Association des sclérodermiques de France (ASF)
  • Groupement Interrégional de Recherche clinique et d’innovation de l’Est (GIRCI-Est).
  • CSL Behring
  • LFB