Project abstract
Background
Societal context of this INFLAMOS 38 project is the growing ageing of the French population increasing the number of patients affected by chronic skeletal degenerative inflammatory diseases. Periodontitis is a highly prevalent degenerative chronic inflammatory disease of tissues surrounding and supporting the tooth and affecting more than 50% of the French adult population, growing up to 70% in adults older than 65 years. Rheumatoid arthritis characterized by joint damages and bone destruction affects millions of persons worldwide and is among the most common causes of disability.
Aim of the project
The main goal of this project is to highlight conceptual proofs on the therapeutic use of IL-38 in two degenerative chronic inflammatory diseases sharing immunopathogenic similarities: periodontitis and rheumatoid arthritis. These diseases affect millions of persons and up to 40% of patients still remain unresponsive to all current treatments.
Therefore, there is an urgent need to identify new pathogenic or protective cytokines and to design new therapeutic strategies. IL-38 is a new member of the IL-1 family showing homologies with IL-1Ra and IL-36Ra that exhibit anti-inflammatory properties in vitro and in vivo.
Expected results
Our working hypothesis is that IL-38 acts as a naturally occurring inhibitor with potential therapeutic effects in these specific immune-mediated degenerative inflammatory diseases. A better understanding of the expression, molecular mode of action and in vivo anti-inflammatory effect of IL-38 using appropriate animal models and samples from affected patients is essential to develop new therapies in regenerative medicine.
Methodology
Endogenous expression of IL-38 will be investigated in cohorts of patients affected by periodontitis or rheumatoid arthritis. We will perform correlations with biological and clinical data of these patients, particularly in patients in remission. Then, a potent therapeutic anti-inflammatory role of IL-38 will be assessed in animal appropriate models of periodontitis and rhumatoid arthritis using an available adeno-associated virus (AAV-IL-38 allowing the overexpression of IL-38) and recombinant IL-38 injections.