title: The IL-17A-producing CD8+ T-cell population in psoriatic lesional skin comprises mucosa-associated invariant T cells and conventional T cells.
abstract: IL-17A is pivotal in the etiology of psoriasis, and CD8(+) T cells with the ability to produce this cytokine (Tc17 cells) are over-represented in psoriatic lesions. Here we demonstrate that the frequency of Tc17 cells in peripheral blood of psoriasis patients correlated with the clinical severity of the disease. Analysis of cutaneous-associated lymphocyte antigen expression showed that the blood Tc17 population contains a significantly higher proportion of cells with skin-homing potential compared with the CD8(+) T-cell population lacking IL-17A/IL-22 expression. IL-17A-producing CD8(+) T cells in blood have previously been reported to belong mainly to the mucosa-associated invariant T-cell (MAIT cell) lineage characterized by TCR Vα7.2 chain, CD161, IL-18Rα, and multidrug transporter ABCB1 expression. We demonstrate the presence of CD8(+) MAIT cells in the dermis and epidermis of psoriatic plaques, as well as healthy skin; however, IL-17A-producing CD8(+) MAIT cells were predominantly found in psoriatic skin. Notably, we observed IL-17A production in a large proportion of psoriatic plaque-derived CD8(+) T cells devoid of MAIT cell characteristics, likely representing conventional CD8(+) T cells. In conclusion, we provide supporting evidence that implicates Tc17 cells in the pathogenesis of psoriasis and describe the presence of innate CD8(+) MAIT cells in psoriatic lesions as an alternative source of IL-17A.
authors.affiliation: Department of Dermatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. Electronic address: m.b.teunissen@amc.uva.nl.
authors.forename: Marcel B M
authors.initials: MBM
authors.lastname: Teunissen
authors.affiliation: Department of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Nataliya G
authors.initials: NG
authors.lastname: Yeremenko
authors.affiliation: Department of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Dominique L P
authors.initials: DLP
authors.lastname: Baeten
authors.affiliation: Department of Dermatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Saskia
authors.initials: S
authors.lastname: Chielie
authors.affiliation: Department of Dermatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Phyllis I
authors.initials: PI
authors.lastname: Spuls
authors.affiliation: Department of Dermatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Menno A
authors.initials: MA
authors.lastname: de Rie
authors.affiliation: Institut Curie, Département de Biologie des Tumeurs, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lantz
authors.affiliation: Department of Dermatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Pieter C M
authors.initials: PCM
authors.lastname: Res
mesh_terms: D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D002452:Cell Count; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism*; D007378:Interleukins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism / Q000473:pathology; D011565:Psoriasis / Q000378:metabolism / Q000473:pathology*; D012189:Retrospective Studies; D012720:Severity of Illness Index; D012867:Skin / Q000378:metabolism / Q000473:pathology*; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology*; D000097043:Interleukin-22
chemical_list: D007371:Interferon-gamma; D020381:Interleukin-17; D007378:Interleukins; D000097043:Interleukin-22