Characterization of the Fungal Immunopeptidome Involved in the Immunopathological Mechanisms of Psoriasis

Overview

Psoriasis is a chronic immune-mediated skin disorder characterized by inflammatory cutaneous plaques and, occasionally, arthritis, affecting 60 million adults and children worldwide. Although a variety of treatments have been developed aimed to relieve the associated symptoms, there is yet no permanent cure for psoriasis. TH17 type immunity, via the production of IL-17A and other pro-inflammatory cytokines, are considered to play a central role in the pathogenesis of this disease. Moreover, experimental evidence obtained in animal models, points to human mycobiota as a trigger for the initiation and/or progression of psoriasis. Therefore, human studies are required to better characterize the major fungi implicated in the local and systemic inflammatory responses, as well as to determine the immunopeptidome that shapes the pathogenic T cell receptor repertoire. We will explore the hypothesis that commensal fungi could participate in the chronic inflammatory immune response underlying the pathogenesis of human psoriasis via the recognition of cutaneous fungal antigens and/or via a gut-skin mycobiome cross-reactive mechanism

The overall aim of the project is : i) to characterize the nature of human local and systemic inflammatory responses against commensal skin and gut fungal species in psoriatic patients (PsoP) and ii) to determine the fungal immunopeptidome that contributes to the shaping of the T cell receptor (TCR) repertoire of skin-infiltrating T cells. The project is divided into four major scientific objectives: 1. To determine the mycobiome profiles in healthy donors (HD) and PsoP. 2. To characterize the contribution of mycobiota to the local cutaneous CD4+ T cell response. 3. To assess systemic the CD4+ T cell-fungal cross-reactivity. 4. To establish the immunopeptidome of the major CD4+ T cell-reactive fungus enabling the development of an innovative immunotherapy.

Conditions