Interaction Between CCR6+ Th17 Cells and CD34+ Fibrocytes Promotes Inflammation: Implications in Graves' Orbitopathy in Chinese Population

被引：34

作者：

Fang, Sijie ^{[1
,2
,3
,4
]}

Huang, Yazhuo ^{[1
,2
,3
,4
]}

Liu, Xingtong ^{[1
,2
]}

Zhong, Sisi ^{[1
,2
]}

Wang, Ningjian ^{[5
]}

Zhao, Binbin ^{[3
,4
,6
]}

Li, Yinwei ^{[1
,2
]}

Sun, Jing ^{[1
,2
]}

Wang, Yang ^{[1
,2
]}

Zhang, Shuo ^{[1
,2
]}

Gu, Ping ^{[1
,2
]}

Zhou, Huifang ^{[1
,2
]}

Li, Bin ^{[2
,3
,4
]}

Fan, Xianqun ^{[1
,2
]}

机构：

[1] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Dept Ophthalmol, Sch Med, 639 Zhizaoju Rd, Shanghai, Peoples R China

[2] Shanghai Key Lab Orbital Dis & Ocular Oncol, Shanghai, Peoples R China

[3] Shanghai Jiao Tong Univ, Sch Med, Shanghai Inst Immunol, Shanghai, Peoples R China

[4] Shanghai Jiao Tong Univ, Sch Med, Dept Immunol & Microbiol, Shanghai, Peoples R China

[5] Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 9, Dept Endocrinol & Metab, Shanghai, Peoples R China

[6] Chinese Acad Sci, CAS Key Lab Mol Virol & Immunol, CAS Ctr Excellence Mol Cell Sci,Unit Mol Immunol, Inst Pasteur Shanghai,Shanghai Inst Biol Sci, Shanghai, Peoples R China

来源：

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE | 2018年 / 59卷 / 06期

基金：

中国国家自然科学基金;

关键词：

CCR6; Th17; cell; fibrocyte; inflammation; Graves' orbitopathy; ORBITAL FIBROBLASTS; CIRCULATING FIBROCYTES; TSH-RECEPTOR; T-CELLS; PATHOGENESIS; DISEASE; OPHTHALMOPATHY; AXIS; MECHANISMS; EXPRESSION;

D O I：

10.1167/iovs.18-24008

中图分类号：

R77 [眼科学];

学科分类号：

100212 ;

摘要：

PURPOSE. Recent reports suggest that Th17 immunity and bone marrow-derived CD34(+) fibrocytes contribute to the pathogenesis of Graves' orbitopathy (GO). This study investigated interactions between Th17 cells and fibrocytes in GO inflammation in Chinese subjects. METHODS. Th17 cells and fibrocytes were derived from blood samples from Chinese GO patients 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 to study inflammatory activity of fibrocytes from GO patients and control subjects. Coculture, quantitative RT-PCR, Luminex, and transwell assays were performed to investigate the relationship between Th17 cells and fibrocytes. RESULTS. CC-chemokine receptor 6 (CCR6(+)) Th17 cells were increased in both active (P < 0.001) and inactive (P < 0.05) GO patients, compared with healthy controls. There was a positive correlation between number of CCR6(+) Th17 cells and GO clinical activity score (P < 0.0001, r = 0.8176). Further, CD34(+) fibrocytes were increased in GO patients, with increased expression of IL-17RA (P < 0.05), CD80 (P < 0.05), and CD86 (P < 0.05). A decreased population of effector Treg cells (P < 0.01) and increased CTLA-4 expression on naive Treg cells (P < 0.05) were observed in GO patients. IL-17A stimulated cytokine production in fibrocytes; GO fibrocytes exhibited more robust production than normal fibrocytes. Autologous Th17 cells promoted inflammatory and antigen-presenting functions of GO fibrocytes; conversely, fibrocytes enhanced Th17 cell-function and recruited Th17 cells in a macrophage inflammatory protein 3 (MIP-3)/CCR6-dependent manner. CONCLUSIONS. The crosstalk between CCR6(+) Th17 cells and fibrocytes plays a role in the pathogenesis of GO. Suppressing these interactions may be a candidate molecular target for therapeutic approaches of GO.

引用

页码：2604 / 2614

页数：11

共 41 条

[1] Current Insights into the Pathogenesis of Graves' Ophthalmopathy [J].