CCR2 enhances CD25 expression by FoxP3^(+) regulatory T cells and regulates their abundance independently of chemotaxis and CCR2^(+) myeloid cells

作     者：Yifan Zhan Nancy Wang Ajithkumar Vasanthakumar Yuxia Zhang Michael Chopin Stephen L.Nutt Axel Kallies Andrew M.Lew 

作者机构：The Walter&Eliza Hall Institute of Medical ResearchParkvilleVIC 3052Australia Department of Medical BiologyUniversity of MelbourneParkvilleVIC 3010Australia Guangzhou Institute of PaediatricsGuangzhou Women and Children’s Medical CentreGuangzhou Medical University510623 GuangzhouGuangdongChina Department of Microbiology and ImmunologyPeter Doherty Institute for Infection and ImmunityUniversity of MelbourneParkvilleVIC 3010Australia 

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2期

页      面：123-132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：We thank M.Dayton,Li Sun,and Lisa Reid for technical assistance This work was supported by the Rebecca L.Cooper Foundation,National Health and Medical Research Council of Australia(NHMRC)grants(1037321,1080321,1105209,1143976) an NHMRC Independent Research Institutes Infrastructure Support Scheme grant(361646) a Victorian State Government Operational Infrastructure Support grant. 

主　　题：CCR2 CD25 organs 

摘      要：A wide array of chemokine receptors,including CCR2,are known to control Treg migration.Here,we report that CCR2 regulates Tregs beyond chemotaxis.We found that CCR2 deficiency reduced CD25 expression by FoxP3^(+) Treg cells.Such a change was also consistently present in irradiation chimeras reconstituted with mixed bone marrow from wild-type(WT)and CCR2−/−strains.Thus,CCR2 deficiency resulted in profound loss of CD25 ^(hi) FoxP3^(+) Tregs in secondary lymphoid organs as well as in peripheral tissues.CCR2−/−Treg cells were also functionally inferior to WT cells.Interestingly,these changes to Treg cells did not depend on CCR2+monocytes/moDCs(the cells where CCR2 receptors are most abundant).Rather,we demonstrated that CCR2 was required for TLR-stimulated,but not TCR-or IL-2-stimulated,CD25 upregulation on Treg cells.Thus,we propose that CCR2 signaling can increase the fitness of FoxP3^(+) Treg cells and provide negative feedback to counter the proinflammatory effects of CCR2 on myeloid cells.