Contact : Cécile Gladine (NUTRIVASC)

Abstract

To regulate the inflammatory response, the body produces two major families of inflammatory mediators: cytokines and oxylipins. These mediators act in concert to initiate the cardinal signs of inflammation and orchestrate its resolution. However, in clinical practice or research, oxylipins are rarely considered, and the inflammatory response remains largely studied solely from the perspective of cytokines. This significantly underestimates the complexity of the human inflammatory response. Consequently, the mechanisms of dysregulated inflammation are still poorly understood, and the management of many disorders in intensive care units, such as severe forms of COVID-19, remains largely supportive. We hypothesize that measuring the host's ability to produce oxylipins in response to immune stimulation has the potential to provide a new diagnostic tool to better understand and manage dysregulated inflammation and patient heterogeneity. Using highly standardized immunophenotyping tools and a cohort of healthy donors well characterized across various dimensions (genotype, lifestyle, etc.), we will first establish what constitutes a healthy oxylipin response and its relationship to the cytokine response. We will then study COVID-19 as a proof-of-concept disease to test our hypothesis.
VARIANCE aims to improve the understanding and clinical management of dysregulated inflammation and its complications. Our research will use oxylipin production by stimulated blood cells as a proxy for assessing the host immune response. The VARIANCE project involves 3 partners (INRAE-UNH; Institut Pasteur-CB UTechS and Institut Pasteur-Translational Immunologie) who bring together (i) complementary and interdisciplinary expertise and skills in oxylipin biology and biochemistry, immunology and variability of the immune response, cell biology, lipidomics, epidemiology and biostatistics and (ii) exceptional resources (state-of-the-art equipment, biocollections and unique data from three clinical studies (the Milieu interieur population study, the St James Covid-19 Bioresources study and the RADIPEM study).

Parteners

UTechS CB UTechS CB - Cytometrie et Biomarqueurs