Lyon 1 University, Lyon, France
CIRI-Centre International de Recherche en Infectiologie ; INSERM, U1111, Univ Lyon, Université de Lyon 1, Ecole Normale Supérieure de Lyon, CNRS, UMR 5308, Lyon, France
Hospices Civils de Lyon, CHU Lyon (Centre Hospitalier Universitaire de Lyon), Allergology and clinical immunology, Lyon, France
SAS Pierre Fabre Dermo Cosmetique, Laboratoires Dermatologiques Ducray, Les Cauquillous, 81506 Lavaur Cedex, France
These authors contributed equally
Psoriasis is a multifactorial skin pathology resulting from genetic susceptibility and environmental triggers that lead to epidermal and immune dysfunction. There is now strong evidence that non-lesional (NL) psoriatic skin, despite its normal appearance, represents an intermediate state between healthy and lesional skin. Changes observed in NL skin mainly affect the skin barrier, keratinocytes, innate and adaptive immune responses, the microbiota and neurogenic tissue innervation. Several epidermal barrier defects are commonly observed in NL skin compared to healthy skin, including an elevated pH, delayed barrier function repair after injury and lower expression of epidermal differentiation complex proteins. NL keratinocytes also show a predisposition for activation and proliferation, and an increased sensitivity to cytokine or microbial triggers, probably linked to their unique transcriptome and proteome, associated with their intermediate state between healthy and lesional cells. In addition, the accumulation of pathogenic IL-17-producing resident memory T cells, which can (re)instigate the formation of new lesions, characterises both the NL and never-lesional skin of patients with psoriasis. Although the contribution of NL skin dysbiosis to psoriasis pathophysiology remains to be clarified, the expression of numerous pruritogenic mediators appears to be involved in disease progression due to an iterative itch–scratch cycle. In summary, the NL skin of patients with psoriasis exhibits numerous hallmarks of dormant psoriasis. The fact that these alterations are mostly located in the epidermis suggests that they are readily accessible to topical treatments, which could prevent the recurrence/spread of this chronic disease.