title: T cells mediate autoantibody-induced cutaneous inflammation and blistering in epidermolysis bullosa acquisita.
abstract: T cells are key players in autoimmune diseases by supporting the production of autoantibodies. However, their contribution to the effector phase of antibody-mediated autoimmune dermatoses, i.e., tissue injury and inflammation of the skin, has not been investigated. In this paper, we demonstrate that T cells amplify the development of autoantibody-induced tissue injury in a prototypical, organ-specific autoimmune disease, namely epidermolysis bullosa acquisita (EBA) - characterized and caused by autoantibodies targeting type VII collagen. Specifically, we show that immune complex (IC)-induced inflammation depends on the presence of T cells - a process facilitated by T cell receptor (TCR)γδ and NKT cells. Because tissue damage in IC-induced inflammation is neutrophil-dependent, we further analyze the interplay between T cells and neutrophils in an experimental model of EBA. We demonstrate that T cells not only enhance neutrophil recruitment into the site of inflammation but also interact with neutrophils in lymphatic organs. Collectively, this study shows that T cells amplify the effector phase of antibody-induced tissue inflammation.
authors.affiliation: Lübeck Institute of Experimental Dermatology (LIED), University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Bieber
authors.affiliation: Lübeck Institute of Experimental Dermatology (LIED), University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany.
authors.forename: Mareike
authors.initials: M
authors.lastname: Witte
authors.affiliation: Lübeck Institute of Experimental Dermatology (LIED), University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany.|Department of Immunology, Dalian Medical University, No9 West Section Lvshun S Rd, Liaoning Province, China.
authors.forename: Shijie
authors.initials: S
authors.lastname: Sun
authors.affiliation: Lübeck Institute of Experimental Dermatology (LIED), University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Hundt
authors.affiliation: Institute of Anatomy, University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Kalies
authors.affiliation: Lübeck Institute of Experimental Dermatology (LIED), University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany.
authors.forename: Sören
authors.initials: S
authors.lastname: Dräger
authors.affiliation: Lübeck Institute of Experimental Dermatology (LIED), University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany.
authors.forename: Anika
authors.initials: A
authors.lastname: Kasprick
authors.affiliation: Lübeck Institute of Experimental Dermatology (LIED), University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany.|Department of Dermatology, Johannes Gutenberg-University Mainz, Saarstraße 21, D-55122 Mainz, Germany.
authors.forename: Trix
authors.initials: T
authors.lastname: Twelkmeyer
authors.affiliation: ISEF, University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany.
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: Manz
authors.affiliation: Institute of Anatomy, University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: König
authors.affiliation: ISEF, University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Köhl
authors.affiliation: Department of Dermatology, University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany.
authors.forename: Detlef
authors.initials: D
authors.lastname: Zillikens
authors.affiliation: Lübeck Institute of Experimental Dermatology (LIED), University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany.|Department of Dermatology, University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany.
authors.forename: Ralf J
authors.initials: RJ
authors.lastname: Ludwig
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000936:Antigen-Antibody Complex / Q000737:chemistry / Q000378:metabolism; D001323:Autoantibodies / Q000096:biosynthesis*; D002450:Cell Communication / Q000276:immunology; D024143:Collagen Type VII / Q000235:genetics / Q000276:immunology; D003412:Cricetulus; D004195:Disease Models, Animal; D016107:Epidermolysis Bullosa Acquisita / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000473:pathology; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology; D011817:Rabbits; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D012867:Skin / Q000276:immunology* / Q000473:pathology; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D001323:Autoantibodies; C583886:Col7a1 protein, mouse; D024143:Collagen Type VII; D007074:Immunoglobulin G; D016692:Receptors, Antigen, T-Cell, gamma-delta