Novel strategies for Osteoarthritis treatment based on innate LYMPhoid Cells modulation

• Applicant: Dr. Irene Mattiola
• Subject Area: Immunology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 529946745

Osteoarthritis (OA) is a painful joint disease affecting over 500 million people worldwide with a considerable socio-economic burden. Due to the absence of efficient therapeutic options and the major public health concerns represented by OA, the World Health Organization (WHO) has included OA in its top priority diseases. Research on OA perfectly matches the United Nations decade of healthy ageing (2021-30) and there are pressing needs for the identification of novel therapeutic strategies. OA is a heterogeneous disease with multiple clinical phenotypes. Three distinct synovial pathotypes were identified by our international consortium which correlated with the clinical features of the patients. Our preliminary data highlighted that the more severe pathotype in OA patients was characterised by the infiltration of distinct innate lymphoid cells (ILC) subsets, and the same observation was valid for a relevant mouse model of OA. ILC accumulation correlated with synovial inflammation, suggesting a role for ILC in regulating synovial immune cell responses. Studies reported a role of the microbiota in shaping the activation of ILC and showed that modifications in the microbiota led to joint pathophysiology and promoted the development of OA, suggesting a potential correlation between ILC/microbiota and OA. Through the ANR PRCI “OLYMPiCS2024” project, and based on strong preliminary data and solid evidence from the literature, our Franco-German consortium aims at: - Deciphering the diversity and spatial distribution of ILC in joint tissues at different stages of OA and the correlation with clinical features of patients. - Investigating the contribution of ILC subsets to the pathophysiology of OA and evaluating therapeutic agents aimed at modulating ILC activation in OA models. - Studying the role of microbiota-dependent regulation of ILC in relevant models of OA, to bring the proof of concept for a diet-based microbiota/ILC-modulating strategy/therapeutic approach in OA dog patients. This project involves the complementary and multidisciplinary expertise of French and German research teams in OA pathophysiology, synovial histopathology and ILC biology in homeostasis and diseases, and in evaluating therapeutic approaches aimed at modulating inflammation and ILC activation in several preclinical models. Overall, OLYMPiC2024 has all the ingredients for advancing scientific and translational research in OA and the potential for proposing therapeutic strategies with a concrete impact on the OA patients’ quality of life.

• DFG Programme: Research Grants
• International Connection: France
• Cooperation Partner: Marie-Astrid Boutet, Ph.D.