CE14 - Physiologie et physiopathologie

B and T cell dialogue in multiple sclerosis physiopathology – BaT-MS

Submission summary

Multiple Sclerosis (MS) is an autoimmune chronic disease of the central nervous system affecting more than 2 million people worldwide. Ninety percent of the patients first develop a form called relapsing remitting MS (RRMS), which is considered acutely inflammatory. But, more than half of these patients develop 15 years after MS onset a progressive disabling form (SPMS) for which no treatments are available. Current RRMS treatments show great success in the first phase of the disease but have no effect to stop disease progression in SPMS patients.

Due to the demonstrated role of B and CD4 T cells in MS physiopathology or in the mouse model of Experimental Autoimmune Encephalomyelitis, which mimics acute phase of RMS, we hypothesize that a better understanding of the immune events associated to the early stages of RRMS could unravel new ways to act on the pathogenic mechanisms of MS and avoid, ultimately, transition to a progressive form.
In this project, our aims are to realize a deep characterization of B and T cell functional heterogeneity, and dynamic of polarization between pro- and anti-inflammatory responses in RRMS in regards to 3 interconnected features: B cell dialogue with T cells, tissue origin, cytokine environment/signaling (especially IL2). A specific focus will be on T follicular helper (Tfh) and T follicular regulatory (Tfr) cells, well-known to modulate B cells responses. Further, preclinical mouse models will be used to determine the in vivo functions and polarization of B, Tfh and Tfr subsets at the onset of the disease in appropriate deficient mice and will be translated ex vivo in organoid human cultures.

Project coordination

Laure Michel (CHRU RENNES)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

INFINITy Institut national de la sante et de la recherche medicale
MOBIDIC U1236 - Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer
DRI CHRU RENNES
ImmunoConcEpT Immunologie Conceptuelle, Expérimentale et Translationnelle

Help of the ANR 696,926 euros
Beginning and duration of the scientific project: December 2022 - 36 Months

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