Interaction Between CCR6þ Th17 Cells and CD34þFibrocytes Promotes Inflammation: Implications inGraves’ Orbitopathy in Chinese Population

Investigative Ophthalmology & Visual Science

article

Sijie Fang¹  Yazhuo Huang¹  Xingtong Liu¹  Sisi Zhong¹  Ningjian Wang⁵  Binbin Zhao³  Yinwei Li¹  Jing Sun¹  Yang Wang¹  Shuo Zhang¹  Ping Gu¹  Huifang Zhou¹  Bin Li²  Xianqun Fan¹ 

[1] Department of Ophthalmology, Shanghai Ninth People"s Hospital, Shanghai JiaoTong University School of Medicine;Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology;Shanghai Institute of Immunology, Shanghai JiaoTong University School of Medicine;Department of Immunology and Microbiology, Shanghai JiaoTong University School of Medicine;Department of Endocrinology and Metabolism, Shanghai Ninth People"s Hospital, Shanghai JiaoTong University School of Medicine;CAS Center for Excellence in Molecular Cell Science, CAS Key Laboratory of Molecular Virology and Immunology, Unit of Molecular Immunology, Institute Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences

关键词: CCR6;    Th17 cell;    fibrocyte;    inflammation;    Graves’ orbitopathy;   

DOI  :  10.1167/iovs.18-24008

学科分类：社会科学、人文和艺术（综合）

来源: Association for Research in Vision and Ophthalmology

【 摘 要 】

PURPOSE. Recent reports suggest that Th17 immunity and bone marrow–derived CD34þfibrocytes contribute to the pathogenesis of Graves’ orbitopathy (GO). This study investigatedinteractions between Th17 cells and fibrocytes in GO inflammation in Chinese subjects.METHODS. Th17 cells and fibrocytes were derived from blood samples from Chinese GOpatients and healthy controls. Proportions and phenotypes of Th17 cells, regulatory T cells(Tregs), and fibrocytes were examined by flow cytometry. Exogenous IL-17A was used tostudy inflammatory activity of fibrocytes from GO patients and control subjects. Coculture,quantitative RT-PCR, Luminex, and transwell assays were performed to investigate therelationship between Th17 cells and fibrocytes.RESULTS. CC-chemokine receptor 6 (CCR6þ) Th17 cells were increased in both active (P <0.001) and inactive (P < 0.05) GO patients, compared with healthy controls. There was apositive correlation between number of CCR6þ Th17 cells and GO clinical activity score (P <0.0001, r ¼ 0.8176). Further, CD34þ fibrocytes were increased in GO patients, with increasedexpression of IL-17RA (P < 0.05), CD80 (P < 0.05), and CD86 (P < 0.05). A decreasedpopulation of effector Treg cells (P < 0.01) and increased CTLA-4 expression on na¨ıve Tregcells (P < 0.05) were observed in GO patients. IL-17A stimulated cytokine production infibrocytes; GO fibrocytes exhibited more robust production than normal fibrocytes.Autologous Th17 cells promoted inflammatory and antigen-presenting functions of GOfibrocytes; conversely, fibrocytes enhanced Th17 cell-function and recruited Th17 cells in amacrophage inflammatory protein 3 (MIP-3)/CCR6-dependent manner.CONCLUSIONS. The crosstalk between CCR6þ Th17 cells and fibrocytes plays a role in thepathogenesis of GO. Suppressing these interactions may be a candidate molecular target fortherapeutic approaches of GO.

【 授权许可】

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