title: Epidermal Th22 and Tc17 cells form a localized disease memory in clinically healed psoriasis.
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 (TRM) cells have been ascribed a role in immunity after resolved viral skin infections. Because of their localization in the epidermal compartment of the skin, TRM may contribute to tissue pathology during psoriasis. In this study, we investigated whether resolved psoriasis lesions contain TRM 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 TRM 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 TRM 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 TRM 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.
authors.affiliation: Department of Medicine Solna, Karolinska Institutet, 171 77 Stockholm, Sweden;
authors.forename: Stanley
authors.initials: S
authors.lastname: Cheuk
authors.forename: Maria
authors.initials: M
authors.lastname: Wikén
authors.forename: Lennart
authors.initials: L
authors.lastname: Blomqvist
authors.forename: Susanne
authors.initials: S
authors.lastname: Nylén
authors.forename: Toomas
authors.initials: T
authors.lastname: Talme
authors.forename: Mona
authors.initials: M
authors.lastname: Ståhle
authors.forename: Liv
authors.initials: L
authors.lastname: Eidsmo
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003879:Dermatologic Agents / Q000627:therapeutic use; D004817:Epidermis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology* / Q000528:radiation effects; D000069285:Infliximab; D039001:Integrin alpha Chains / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018613:Microscopy, Confocal; D008875:Middle Aged; D018448:Models, Immunological; D011565:Psoriasis / Q000188:drug therapy / Q000276:immunology* / Q000532:radiotherapy; D054399:Receptors, CCR6 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018123:Receptors, Interleukin / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D059467:Transcriptome / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D014466:Ultraviolet Rays; D000069549:Ustekinumab; D055815:Young Adult; D000097043:Interleukin-22
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D003879:Dermatologic Agents; D000069285:Infliximab; D039001:Integrin alpha Chains; D020381:Interleukin-17; D007378:Interleukins; D054399:Receptors, CCR6; D018123:Receptors, Interleukin; D000069549:Ustekinumab; D000097043:Interleukin-22; C106311:CCR6 protein, human; C515500:IL23R protein, human; C091367:alpha E integrins