CE17 - Recherche translationnelle en santé

Variability of Immunomodulating oxylipins biosynthesis and its impact on the severity of COVID-19 disease. – VARIANCE

Submission summary

To regulate inflammatory response, the host produces two main families of inflammatory mediators that are the cytokines and the oxylipins. These mediators act in concert to initiate the cardinal signs of inflammation and orchestrate its resolution. However, in clinics or in research, oxylipins are largely overlooked and the inflammatory response remains mostly studied only in the context of cytokine production. This considerably underestimates the complexity of the inflammatory response. Consequently, we still have a poor understanding of the mechanisms of dysregulated inflammation and the management of many ICU-related disorders such as the severe complications of COVID-19 disease remains mostly supportive.
We hypothesize that the assessing capacity of the host to produce oxylipins in response to an immune insult could provide a potential new tool to better understand and assess dysregulated inflammation and patient heterogeneity. Using highly standardized immunophenotyping tools and a well-defined healthy donor cohort, we will first characterize the healthy oxylipin response and how it is co-regulated in parallel to cytokine responses. We will then study COVID-19 as a proof of concept disease to test our hypothesis.
VARIANCE aims at improving the understanding and clinical management of dysregulated inflammation and associated complications. Our investigations will be based on the production of oxylipins by stimulated whole blood (WB) cells used as a proxy to assess host immune responsiveness.
The VARIANCE project involves 3 partners (INRAE-UNH; Institut Pasteur-CB UTechS and Institut Pasteur-Translational Immunologie) who gathers complementary and interdisciplinary expertise and skills in biology & biochemistry of oxylipins, immunology & variability of the immune response, cell biology, MS-based lipidomics, epidemiology and biostatistics. It also has outstanding resources including cutting-edge equipments and unique biocollections and data warehouse from three clinical studies (i.e. the Milieu Interieur population study, St James Covid-19 Bioresources and the RADIPEM studies).

Project coordinator

Madame Cécile Gladine (Unité de Nutrition Humaine)

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

UTechS CB UTechS CB - Cytometrie et Biomarqueurs
UNH Unité de Nutrition Humaine
UTechS CB UTechS CB - Cytometrie et Biomarqueurs

Help of the ANR 673,295 euros
Beginning and duration of the scientific project: January 2023 - 36 Months

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