Keratinocytes costimulate naive human T cells via CD2: a potential target to prevent the development of proinflammatory Th1 cells in the skin

作     者：Christian Orlik Daniel Deibel Johanna Küblbeck Emre Balta Sabina Ganskih Jüri Habicht Beate Niesler Jutta Schröder-Braunstein Knut Schäkel Guido Wabnitz Yvonne Samstag 

作者机构：Institute of ImmunologySection Molecular ImmunologyHeidelberg UniversityIm Neuenheimer Feld 30569120 HeidelbergGermany Institute of Human GeneticsDepartment of Human Molecular Geneticsand nCounter Core FacilityHeidelberg UniversityIm Neuenheimer Feld 36669120 HeidelbergGermany Department of DermatologyHeidelberg UniversityIm Neuenheimer Feld 44069120 HeidelbergGermany 

出 版 物：《Cellular & Molecular Immunology》 (中国免疫学杂志（英文版）)

年 卷 期：2020年第17卷第4期

页      面：380-394页

核心收录：

学科分类：0710[理学-生物学] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100102[医学-免疫学] 10[医学] 

基　　金：supported by a grant from the German Research Foundation(SFB CRC156 project B04 and INST 114089/31-1 FUGG to Y.S.). 

主　　题：keratinocytes inflammatory skin diseases psoriasis human T cells costimulation CD2 LFA-1 nonprofessional antigenpresenting cells Th1 cells Th17 cells 

摘      要：The interplay between keratinocytes and immune cells,especially T cells,plays an important role in the pathogenesis of chronic inflammatory skin diseases.During psoriasis,keratinocytes attract T cells by releasing chemokines,while skin-infiltrating selfreactive T cells secrete proinflammatory cytokines,e.g.,IFN γand IL-17A,that cause epidermal hyperplasia.Similarly,in chronic graftversus-host disease,allogenic IFN γ-producing Th1/Tc1 and IL-17-producing Th17/Tc17 cells are recruited by keratinocyte-derived chemokines and accumulate in the skin.However,whether keratinocytes act as nonprofessional antigen-presenting cells to directly activate naive human T cells in the epidermis remains unknown.Here,we demonstrate that under proinflammatory conditions,primary human keratinocytes indeed activate naive human T cells.This activation required cell contact and costimulatory signaling via CD58/CD2 and CD54/LFA-1.Naive T cells costimulated by keratinocytes selectively differentiated into Th1 and Th17 cells.In particular,keratinocyte-initiated Th1 differentiation was dependent on costimulation through CD58/CD2.The latter molecule initiated STAT1 signaling and IFN γproduction in T cells.Costimulation of T cells by keratinocytes resulting in Th1 and Th17 differentiation represents a new explanation for the local enrichment of Th1 and Th17 cells in the skin of patients with a chronic inflammatory skin disease.Consequently,local interference with T cell–keratinocyte interactions may represent a novel strategy for the treatment of Th1 and Th17 cell-driven skin diseases.