Shortening Treatments Of Chronic Inflammatory Conditions

Background Psoriasis is a common disease which is a source of major distress for patients and costs for the society. Treatments are effective but temporary and relapses occur, preferentially at sites previously involved. Locally, tissue resident memory T cells (TRM) cells prone to produce pathogenic cytokines accumulate in the outer layers of the resolved skin of psoriasis patients under treatment, and can trigger strong inflammatory responses upon reactivation, thus starting the cascade of the relapse. We have recently shown that the skin transcriptional responses after TRM cell activation in healed skin biopsies of patients could predict the time until the disease relapse. How to modify the local pool of TRM cells in the human skin is not known, but several factors leading to the establishment and the persistence of the TRM cells in the skin are suggested. First, the skin microbiota has emerged as a potent actor of the skin immunity, with the capacity to shape the pool of skin T cells in mice. Second, after TRM cells are settled in the skin, their lipid intake will impact their local survival. Last, in addition to these local factors, the gut subclinical inflammation that lead to bacterial translocation can trigger a more global state of inflammation in the body and could drive the local survival of the TRM cells in the skin. Aims Our first aim in this project is to validate a tool to predict psoriasis relapse upon treatment withdrawal in a cohort of patients treated with systemic drugs- the STOPso cohort (Shortening Treatments Of Psoriasis). We will correlate the skin reaction to local TRM activation in resolved lesions to the time before relapse. In parallel, we will characterize several factors likely to participate to the establishment, function and survival of the TRM cells in the skin. We will decipher the skin microbiota and mycobiota; the lipid composition of the outer layer of the skin; the presence of lipopolysaccharide in the blood, in order to better