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RESEARCH PRODUCT

T cells mediate autoantibody-induced cutaneous inflammation and blistering in epidermolysis bullosa acquisita

Kathrin KaliesMareike WitteRalf LudwigShijie SunShijie SunPeter KönigSören DrägerDetlef ZillikensJennifer E. HundtKatja BieberRudolf A. ManzAnika KasprickJörg KöhlTrix TwelkmeyerTrix Twelkmeyer

subject

0301 basic medicineEpidermolysis bullosa acquisitamedicine.medical_specialtyCollagen Type VIINeutrophilsT-LymphocytesGene ExpressionMice NudeInflammationAntigen-Antibody ComplexCell CommunicationEpidermolysis Bullosa AcquisitaArticleMice03 medical and health sciencesCricetulus0302 clinical medicinemedicineAnimalsHumansAutoantibodiesSkinAutoimmune diseaseMice Inbred BALB CMultidisciplinarybusiness.industryT-cell receptorAutoantibodyAntibodies MonoclonalReceptors Antigen T-Cell gamma-deltamedicine.diseaseNatural killer T cellDermatologyImmune complexMice Inbred C57BLDisease Models Animal030104 developmental biologyLymphatic systemImmunoglobulin GImmunologyNatural Killer T-CellsLymph NodesRabbitsmedicine.symptombusinessSpleenSignal Transduction030215 immunology

description

AbstractT 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.

yearjournalcountryeditionlanguage
2016-12-05Scientific Reports
https://doi.org/10.1038/srep38357