Frontiers in Immunology (Jun 2018)
Signal Transducer and Activator of Transcription 3 Hyperactivation Associates With Follicular Helper T Cell Differentiation and Disease Activity in Rheumatoid Arthritis
- Jun Deng,
- Jun Deng,
- Jun Deng,
- Chaofan Fan,
- Xin Gao,
- Xin Gao,
- Xin Gao,
- Qunxiong Zeng,
- Qunxiong Zeng,
- Ruru Guo,
- Yunbo Wei,
- Zhian Chen,
- Zhian Chen,
- Yanan Chen,
- Dongcheng Gong,
- Dongcheng Gong,
- Jia Feng,
- Yan Xia,
- Shifei Xiang,
- Shushi Gong,
- Lin Yuan,
- Wei Shen,
- Wenyan Shen,
- Lin Lin,
- Ting Jiang,
- Dongyi He,
- Liangjing Lu,
- Xiaoxiang Chen,
- Di Yu,
- Di Yu,
- Di Yu,
- Di Yu,
- Di Yu
Affiliations
- Jun Deng
- China-Australia Centre for Personalised Immunology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Jun Deng
- Department of Rheumatology, Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Jun Deng
- Hubei Provincial Key Laboratory of Occurrence and Intervention of Rheumatic Diseases, Affiliated Hospital of Hubei University for Nationalities, Enshi, China
- Chaofan Fan
- Department of Rheumatology, Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Xin Gao
- China-Australia Centre for Personalised Immunology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Xin Gao
- Department of Rheumatology, Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Xin Gao
- Department of Immunology and Infectious Disease, John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia
- Qunxiong Zeng
- China-Australia Centre for Personalised Immunology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Qunxiong Zeng
- Department of Rheumatology, Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Ruru Guo
- Department of Rheumatology, Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Yunbo Wei
- Laboratory of Immunology for Environment and Health, Shandong Analysis and Test Center, Qilu University of Technology, Shandong Academy of Sciences, Jinan, China
- Zhian Chen
- China-Australia Centre for Personalised Immunology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Zhian Chen
- Department of Immunology and Infectious Disease, John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia
- Yanan Chen
- Department of Rheumatology, Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Dongcheng Gong
- China-Australia Centre for Personalised Immunology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Dongcheng Gong
- Department of Rheumatology, Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Jia Feng
- Department of Rheumatology, Affiliated Hospital of Hubei University for Nationalities, Enshi, China
- Yan Xia
- Department of Rheumatology, Affiliated Hospital of Hubei University for Nationalities, Enshi, China
- Shifei Xiang
- Department of Rheumatology, Affiliated Hospital of Hubei University for Nationalities, Enshi, China
- Shushi Gong
- Department of Rheumatology, Affiliated Hospital of Hubei University for Nationalities, Enshi, China
- Lin Yuan
- Hubei Provincial Key Laboratory of Occurrence and Intervention of Rheumatic Diseases, Affiliated Hospital of Hubei University for Nationalities, Enshi, China
- Wei Shen
- Department of Laboratory Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Wenyan Shen
- Department of Laboratory Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Lin Lin
- Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Ting Jiang
- Guanghua Hospital of Integrative Chinese and Western Medicine, Shanghai, China
- Dongyi He
- Guanghua Hospital of Integrative Chinese and Western Medicine, Shanghai, China
- Liangjing Lu
- Department of Rheumatology, Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Xiaoxiang Chen
- Department of Rheumatology, Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Di Yu
- China-Australia Centre for Personalised Immunology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Di Yu
- Department of Rheumatology, Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Di Yu
- Hubei Provincial Key Laboratory of Occurrence and Intervention of Rheumatic Diseases, Affiliated Hospital of Hubei University for Nationalities, Enshi, China
- Di Yu
- Department of Immunology and Infectious Disease, John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia
- Di Yu
- Laboratory of Immunology for Environment and Health, Shandong Analysis and Test Center, Qilu University of Technology, Shandong Academy of Sciences, Jinan, China
- DOI
- https://doi.org/10.3389/fimmu.2018.01226
- Journal volume & issue
-
Vol. 9
Abstract
Follicular helper T (Tfh) cells are the specialized CD4+ T cell subset that supports B cells to produce high-affinity antibodies and generate humoral memory. Not only is the function of Tfh cells instrumental to mount protect antibodies but also to support autoantibody production and promote systemic inflammation in autoimmune diseases. However, it remains unclear how the activation of Tfh cells is driven in autoimmune diseases. Here, we report that in patients with rheumatoid arthritis (RA), excessive generation of CXCR5+PD-1+ memory Tfh cells was observed and the frequency of memory Tfh cells correlated with disease activity score calculator for RA (DAS28). The differentiation of Tfh cells is dependent on signal transducer and activator of transcription 3 (STAT3), the key transcription factor downstream of cytokine signal pathways. A drastic increase of phosphorylated STAT3 (pSTAT3) in CD4+ T cells were detected in RA patients who also produced larger amounts of STAT3-stimulating cytokines, including IL-6, IL-21, IL-10, and leptin than those of healthy controls. Importantly, the phosphorylation status of STAT3 in CD4+ T cells positively correlated with the plasma concentration of IL-6 and the frequency of memory Tfh cells. This study reveals an IL-6-pSTAT3-Tfh immunoregulatory axis in the pathogenesis of RA and reinforces its candidature as biomarkers and targets for diagnosis and therapy.
Keywords
- rheumatoid arthritis
- patient
- follicular helper T cells
- signal transducer and activator of transcription 3
- phosphorylation
- IL-6
