PsoFungi

Psoriasis is a chronic immune-mediated skin disorder characterized by inflammatory cutaneous plaques and, occasionally, arthritis, affecting 60 million people. Although a variety of treatments have been developed, there is yet no permanent cure. Experimental evidence obtained in animal models, points to the mycobiota as a trigger for the initiation and/or progression of psoriasis. Analysis of cutaneous T cells from healthy individuals has revealed that not only cutaneous, but also intestinal, commensal fungi might contribute to the local response suggesting a causal link between gut and skin immunity. The notion of a skin-gut axis implicated in psoriatic lesions is also supported by the strong association between the occurrence of intestinal diseases and psoriasis. Although the immunological mechanisms remain unknown, recent findings concerning the gut-lung axis involve protective Th17 responses against gut pathobionts in the pathogenesis of non-intestinal immune diseases via a fungal cross-reactive mechanism. Hence, its contribution to the psoriasis inflammatory systemic response should be explored. Current knowledge supports that commensal fungi could contribute to local and systemic inflammation. Nevertheless, understanding of the consequences of fungal-host immune system interactions on the pathogenesis of psoriasis is still rather limited and the relevance of experimental animal is questionable. Consequently, studies based on human samples are required to unravel the mechanisms contributing to the pathogenesis of human psoriasis. We have stablished a consortium of experts on psoriasis, mycobiota and T cell biology to identify commensal fungi implicated in psoriasis pathogenesis based on their ability to shape T cell repertoires observed in patients. Establishment of the immunopeptidome would provide the basis for the development of novel immunotherapies allowing the restoration of the homeostatic immune function by fungal-peptide-desensitization therapies.