title: CD49a Expression Defines Tissue-Resident CD8+T Cells Poised for Cytotoxic Function in Human Skin.
abstract: Tissue-resident memory T (Trm) cells form a heterogeneous population that provides localized protection against pathogens. Here, we identify CD49a as a marker that differentiates CD8+Trm cells on a compartmental and functional basis. In human skin epithelia, CD8+CD49a+Trm cells produced interferon-γ, whereas CD8+CD49a-Trm cells produced interleukin-17 (IL-17). In addition, CD8+CD49a+Trm cells from healthy skin rapidly induced the expression of the effector molecules perforin and granzyme B when stimulated with IL-15, thereby promoting a strong cytotoxic response. In skin from patients with vitiligo, where melanocytes are eradicated locally, CD8+CD49a+Trm cells that constitutively expressed perforin and granzyme B accumulated both in the epidermis and dermis. Conversely, CD8+CD49a-Trm cells from psoriasis lesions predominantly generated IL-17 responses that promote local inflammation in this skin disease. Overall, CD49a expression delineates CD8+Trm cell specialization in human epithelial barriers and correlates with the effector cell balance found in distinct inflammatory skin diseases.
authors.affiliation: Department of Medicine Solna, Karolinska Institutet, Stockholm 171 77, Sweden.
authors.forename: Stanley
authors.initials: S
authors.lastname: Cheuk
authors.affiliation: Center for Hematology and Regenerative Medicine, Department of Medicine Huddinge, Karolinska Institutet, Stockholm 171 77, Sweden.
authors.forename: Heinrich
authors.initials: H
authors.lastname: Schlums
authors.affiliation: Department of Medicine Solna, Karolinska Institutet, Stockholm 171 77, Sweden; Dermatology Department, Karolinska University Hospital, Stockholm 141 86, Sweden.
authors.forename: Irène
authors.initials: I
authors.lastname: Gallais Sérézal
authors.affiliation: Department of Medicine Solna, Karolinska Institutet, Stockholm 171 77, Sweden.
authors.forename: Elisa
authors.initials: E
authors.lastname: Martini
authors.affiliation: Center for Hematology and Regenerative Medicine, Department of Medicine Huddinge, Karolinska Institutet, Stockholm 171 77, Sweden.
authors.forename: Samuel C
authors.initials: SC
authors.lastname: Chiang
authors.affiliation: Dermatology Department, Karolinska University Hospital, Stockholm 141 86, Sweden.
authors.forename: Nicole
authors.initials: N
authors.lastname: Marquardt
authors.affiliation: Department of Medicine Solna, Karolinska Institutet, Stockholm 171 77, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Gibbs
authors.affiliation: Department of Medicine Solna, Karolinska Institutet, Stockholm 171 77, Sweden.
authors.forename: Ebba
authors.initials: E
authors.lastname: Detlofsson
authors.affiliation: Department of Medicine Solna, Karolinska Institutet, Stockholm 171 77, Sweden.
authors.forename: Andrea
authors.initials: A
authors.lastname: Introini
authors.affiliation: Dermatology Department, Karolinska University Hospital, Stockholm 141 86, Sweden.
authors.forename: Marianne
authors.initials: M
authors.lastname: Forkel
authors.affiliation: Unit for Inflammation, Gastroenterology and Rheumatology, Department of Medicine, Huddinge, Karolinska Institutet, Stockholm 171 77, Sweden.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Höög
authors.affiliation: Department of Medicine Solna, Karolinska Institutet, Stockholm 171 77, Sweden.
authors.forename: Annelie
authors.initials: A
authors.lastname: Tjernlund
authors.affiliation: Dermatology Department, Karolinska University Hospital, Stockholm 141 86, Sweden.
authors.forename: Jakob
authors.initials: J
authors.lastname: Michaëlsson
authors.affiliation: Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Building 208, DK-2800 Kongens Lyngby 2800, Denmark.
authors.forename: Lasse
authors.initials: L
authors.lastname: Folkersen
authors.affiliation: Dermatology Department, Karolinska University Hospital, Stockholm 141 86, Sweden.
authors.forename: Jenny
authors.initials: J
authors.lastname: Mjösberg
authors.affiliation: Unit for Endocrinology and Diabetes, Department of Medicine, Huddinge, Karolinska Institutet, Stockholm 171 77, Sweden.
authors.forename: Lennart
authors.initials: L
authors.lastname: Blomqvist
authors.affiliation: Department of Reconstructive Plastic Surgery, Karolinska University Hospital Solna, Stockholm 171 76, Sweden.
authors.forename: Marcus
authors.initials: M
authors.lastname: Ehrström
authors.affiliation: Department of Medicine Solna, Karolinska Institutet, Stockholm 171 77, Sweden; Dermatology Department, Karolinska University Hospital, Stockholm 141 86, Sweden.
authors.forename: Mona
authors.initials: M
authors.lastname: Ståhle
authors.affiliation: Center for Hematology and Regenerative Medicine, Department of Medicine Huddinge, Karolinska Institutet, Stockholm 171 77, Sweden; Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Bergen 5021, Norway. Electronic address: yenan.bryceson@ki.se.
authors.forename: Yenan T
authors.initials: YT
authors.lastname: Bryceson
authors.affiliation: Department of Medicine Solna, Karolinska Institutet, Stockholm 171 77, Sweden; Dermatology Department, Karolinska University Hospital, Stockholm 141 86, Sweden. Electronic address: liv.eidsmo@ki.se.
authors.forename: Liv
authors.initials: L
authors.lastname: Eidsmo
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002469:Cell Separation; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D039423:Integrin alpha1 / Q000096:biosynthesis / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D018613:Microscopy, Confocal; D011565:Psoriasis / Q000276:immunology; D012867:Skin / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014820:Vitiligo / Q000276:immunology
chemical_list: D039423:Integrin alpha1
keywords: CD49a; IL-15; Skin; cytotoxicity; granzyme B; immunopathology; perforin; psoriasis; tissue resident T cells; vitiligo