The research program of Inserm U1234 focuses on the immunopathology and the biotherapy of autoimmune diseases. Autoimmunity and its regulation are studied in physiological and pathological contexts, through murine models and clinical studies. The program which aims to better comprehend the pathophysiology, to develop novel diagnostic tools and to implement innovative therapeutic approaches in the field of autoimmune diseases, is divided into two thematic areas (A).

A1. The first one centers on the study of the pathophysiological mechanisms and the response to treatment of autoimmune neuromuscular (myositis, multiple sclerosis) and skin (pemphigus) diseases. It lies in the development and the analyses of murine models as well as in preclinical studies. The mechanisms studied concern the absence of tolerance towards the autoantigens, the single-cell analyses of autoreactive B cell response and the pathogenicity of autoantibodies isolated from patients and transferred to the animals. New diagnostic immuno-assays are developed and applied to the clinic. In addition, the objective is also to decipher the immuno-regulatory properties of different molecules (ectonucleotides (ATP, NAD), neuropeptides (VIP, PACAP and analogs), nanobodies targeting those pathways) in the aforementioned experimental models.

L'axe A2 a un objectif thérapeutique. Des biothérapies innovantes sont développées au plan préclinique et à travers des essais cliniques. Des projets en développement concernent la thérapie par myoblastes ou par cellules souches du tissu adipeux (myosite à inclusions, sclérodermie systémique, dystrophie musculaire oculopharyngée, rhizarthrose), la thérapie cellulaire de la cornée, et la thérapie par lymphocytes T génétiquement modifiés (CAR-T) avec mise en place d’un modèle préclinique. Des stratégies de surveillance des traitements par biomédicaments sont élaborées et validées dans les contextes de l’auto-immunité et de la transplantation.

The achievement of this program relies on technical facilities of the unit (animal housing, L2 cell culture room, cytometry platform) and of the IRIB (Institute for Research and Innovation in Biomedicine) such as animal facility, transcriptomic/proteomic/mass spectroscopy analysis platforms, NGS sequencing.

The program benefits from several hospital services of the CHU of Rouen (Immunology-Biotherapy, Dermatology, Plastic Surgery, Ophthalmology, Immuno-Pediatric, Internal Medicine, Rheumatology and Pharmacy) allowing studies with patients and bio-banks of tissues. INSERM U1234 is a founding member of the FHU SURFACE and part of the LARC Neurosciences network.

 

Immuno-regulation, autoimmune neuromuscular diseases, myositis, pemphigus, cell therapy