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 

机构地区：[1]Institute of Immunology,Section Molecular Immunology,Heidelberg University,Im Neuenheimer Feld 305,69120 Heidelberg,Germany [2]Institute of Human Genetics,Department of Human Molecular Genetics,and nCounter Core Facility,Heidelberg University,Im Neuenheimer Feld 366,69120 Heidelberg,Germany [3]Department of Dermatology,Heidelberg University,Im Neuenheimer Feld 440,69120 Heidelberg,Germany

出　　处：《Cellular & Molecular Immunology》2020年第4期380-394,共15页中国免疫学杂志（英文版）

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

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.

关 键 词：KERATINOCYTES inflammatory skin diseases psoriasis human T cells COSTIMULATION CD2 LFA-1 nonprofessional antigenpresenting cells Th1 cells Th17 cells 

分 类 号：R392[医药卫生—免疫学]