[HTML][HTML] Epidermal Th22 and Tc17 cells form a localized disease memory in clinically healed psoriasis

S Cheuk, M Wikén, L Blomqvist, S Nylén… - The Journal of …, 2014 - journals.aai.org
S Cheuk, M Wikén, L Blomqvist, S Nylén, T Talme, M Stĺhle, L Eidsmo
The Journal of Immunology, 2014journals.aai.org
Psoriasis is a common and chronic inflammatory skin disease in which T cells play a key
role. Effective treatment heals the skin without scarring, but typically psoriasis recurs in
previously affected areas. A pathogenic memory within the skin has been proposed, but the
nature of such site-specific disease memory is unknown. Tissue-resident memory T (T RM)
cells have been ascribed a role in immunity after resolved viral skin infections. Because of
their localization in the epidermal compartment of the skin, T RM may contribute to tissue …
Abstract
Psoriasis is a common and chronic inflammatory skin disease in which T cells play a key role. Effective treatment heals the skin without scarring, but typically psoriasis recurs in previously affected areas. A pathogenic memory within the skin has been proposed, but the nature of such site-specific disease memory is unknown. Tissue-resident memory T (T RM) cells have been ascribed a role in immunity after resolved viral skin infections. Because of their localization in the epidermal compartment of the skin, T RM may contribute to tissue pathology during psoriasis. In this study, we investigated whether resolved psoriasis lesions contain T RM cells with the ability to maintain and potentially drive recurrent disease. Three common and effective therapies, narrowband-UVB treatment and long-term biologic treatment systemically inhibiting TNF-α or IL-12/23 signaling were studied. Epidermal T cells were highly activated in psoriasis and a high proportion of CD8 T cells expressed T RM markers. In resolved psoriasis, a population of cutaneous lymphocyte–associated Ag, CCR6, CD103, and IL-23R expressing epidermal CD8 T cells was highly enriched. Epidermal CD8 T cells expressing the T RM marker CD103 responded to ex vivo stimulation with IL-17A production and epidermal CD4 T cells responded with IL-22 production after as long as 6 y of TNF-α inhibition. Our data suggest that epidermal T RM cells are retained in resolved psoriasis and that these cells are capable of producing cytokines with a critical role in psoriasis pathogenesis. We provide a potential mechanism for a site-specific T cell–driven disease memory in psoriasis.
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