title: The antimicrobial peptide LL37 is a T-cell autoantigen in psoriasis.
abstract: Psoriasis is a common T-cell-mediated skin disease with 2-3% prevalence worldwide. Psoriasis is considered to be an autoimmune disease, but the precise nature of the autoantigens triggering T-cell activation remains poorly understood. Here we find that two-thirds of patients with moderate-to-severe plaque psoriasis harbour CD4(+) and/or CD8(+) T cells specific for LL37, an antimicrobial peptide (AMP) overexpressed in psoriatic skin and reported to trigger activation of innate immune cells. LL37-specific T cells produce IFN-γ, and CD4(+) T cells also produce Th17 cytokines. LL37-specific T cells can infiltrate lesional skin and may be tracked in patients blood by tetramers staining. Presence of circulating LL37-specific T cells correlates significantly with disease activity, suggesting a contribution to disease pathogenesis. Thus, we uncover a role of LL37 as a T-cell autoantigen in psoriasis and provide evidence for a role of AMPs in both innate and adaptive immune cell activation.
authors.affiliation: 1] Department of Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità, 00100 Rome, Italy [2] Department of Dermatology, University Hospital CHUV, 1011 Lausanne, Switzerland.
authors.forename: Roberto
authors.initials: R
authors.lastname: Lande
authors.affiliation: Dermatology Unit, NESMOS Department, Sapienza University of Rome, 00100 Rome, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Botti
authors.affiliation: Translational tumor immunology group, Ludwig center for cancer research of the University of Lausanne, Lausanne 1066, Switzerland.
authors.forename: Camilla
authors.initials: C
authors.lastname: Jandus
authors.affiliation: TC Metrix, Epalinge 1066, Switzerland.
authors.forename: Danijel
authors.initials: D
authors.lastname: Dojcinovic
authors.affiliation: Department of Biology and Biotechnology 'C. Darwin', University La Sapienza, Rome, 00100 Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Fanelli
authors.affiliation: Department of Dermatology, University Hospital CHUV, 1011 Lausanne, Switzerland.
authors.forename: Curdin
authors.initials: C
authors.lastname: Conrad
authors.affiliation: Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Georgios
authors.initials: G
authors.lastname: Chamilos
authors.affiliation: Department of Dermatology, University Hospital CHUV, 1011 Lausanne, Switzerland.
authors.forename: Laurence
authors.initials: L
authors.lastname: Feldmeyer
authors.affiliation: Department of Dermatology, University Tor Vergata, 00100 Rome, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Marinari
authors.affiliation: Department of Dermatology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Chon
authors.affiliation: Department of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Luis
authors.initials: L
authors.lastname: Vence
authors.affiliation: Division of Rheumatology, Department of Clinical Medicine and Therapy, University La Sapienza, 00100 Rome, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Riccieri
authors.affiliation: TC Metrix, Epalinge 1066, Switzerland.
authors.forename: Phillippe
authors.initials: P
authors.lastname: Guillaume
authors.affiliation: Department of Dermatology, University Hospital of Zurich, 8091 Zurich, Switzerland.
authors.forename: Alex A
authors.initials: AA
authors.lastname: Navarini
authors.affiliation: TC Metrix, Epalinge 1066, Switzerland.
authors.forename: Pedro
authors.initials: P
authors.lastname: Romero
authors.affiliation: 1] Dermatology Unit, NESMOS Department, Sapienza University of Rome, 00100 Rome, Italy [2] Translational tumor immunology group, Ludwig center for cancer research of the University of Lausanne, Lausanne 1066, Switzerland.
authors.forename: Antonio
authors.initials: A
authors.lastname: Costanzo
authors.affiliation: Department of Biology and Biotechnology 'C. Darwin', University La Sapienza, Rome, 00100 Italy.
authors.forename: Enza
authors.initials: E
authors.lastname: Piccolella
authors.affiliation: Department of Dermatology, University Hospital CHUV, 1011 Lausanne, Switzerland.
authors.forename: Michel
authors.initials: M
authors.lastname: Gilliet
authors.affiliation: 1] Department of Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità, 00100 Rome, Italy [2] Department of Dermatology, University Hospital CHUV, 1011 Lausanne, Switzerland.
authors.forename: Loredana
authors.initials: L
authors.lastname: Frasca
mesh_terms: D023181:Antimicrobial Cationic Peptides; D001324:Autoantigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D054804:Cathelicidins / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D011565:Psoriasis / Q000276:immunology*; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D023181:Antimicrobial Cationic Peptides; D001324:Autoantigens; D054804:Cathelicidins