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Basic and translational research
Extended report
Chemotaxis of Vδ2 T cells to the joints contributes to the pathogenesis of rheumatoid arthritis
  1. Wen-Xiu Mo1,
  2. Shan-Shan Yin1,
  3. Hua Chen1,
  4. Chen Zhou1,
  5. Jia-Xin Zhou1,
  6. Li-Dan Zhao1,
  7. Yun-Yun Fei1,
  8. Hua-Xia Yang1,
  9. Jing-Bo Guo2,
  10. Yu-Jia Mao3,
  11. Lin-Fang Huang1,
  12. Wen-Jie Zheng1,
  13. Wen Zhang1,
  14. Jian-Min Zhang3,
  15. Wei He3,
  16. Xuan Zhang1
  1. 1Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Clinical Immunology Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Ministry of Education Key Laboratory, Beijing, China
  2. 2Department of Traditional Chinese Medicine, 256th Clinical Department of Bethune International Peace Hospital of PLA, Shijiazhuang, China
  3. 3Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Medical Molecular Biology, Beijing, China
  1. Correspondence to Professor Xuan Zhang, Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Clinical Immunology Center, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Shuai-Fu-Yuan, Dong-Cheng District, Beijing 100730, China; zxpumch2003{at}sina.com and Dr Wei He, Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Medical Molecular Biology, Beijing, China; hewei{at}ngd.org.cn

Abstract

Objectives To explore the role of Vδ2 T cells in the pathogenesis of rheumatoid arthritis (RA).

Methods Sixty-eight patients with RA, 21 patients with osteoarthritis and 21 healthy controls were enrolled in the study. All patients with RA fulfilled the 2010 American College of Rheumatology/European League Against Rheumatism criteria for RA. Peripheral Vδ2T population, chemokine receptor expression and proinflammatory cytokine secretion were quantified by flow cytometry. The infiltration of Vδ2 T cells within the synovium was examined by immunohistochemistry and flow cytometry. The effect of tumour necrosis factor (TNF)-α and interleukin (IL)-6 on Vδ2 T migration was determined by flow cytometry and transwell migration assay.

Results Peripheral Vδ2T cells, but not Vδ1 T cells, were significantly lower in patients with RA, which was negatively correlated with disease activity gauged by Disease Activity Score in 28 joints. Vδ2 T cells from RA accumulated in the synovium and produced high levels of proinflammatory cytokines including interferon-γ and IL-17. Phenotypically, Vδ2 T cells from RA showed elevated chemotaxis potential and expressed high levels of chemokine receptors CCR5 and CXCR3, which was driven by increased serum TNF-α through nuclear factor kappa B signalling. In vivo, TNF-α neutralising therapy dramatically downregulated CCR5 and CXCR3 on Vδ2 T cells and repopulated the peripheral Vδ2 T cells in patients with RA.

Conclusions High levels of TNF-α promoted CCR5 and CXCR3 expression in Vδ2 T cells from RA, which potentially infiltrated into the synovium and played crucial roles in the pathogenesis of RA. Targeting Vδ2 T cells might be a potential approach for RA.

  • rheumatoid arthritis
  • anti-TNF
  • T cells

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/annrheumdis-2016-211069

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    Footnotes

    • W-XM, S-SY and HC contributed equally.

    • Handling editor Tore K Kvien

    • Contributors W-XM, S-SY and HC contributed equally to this manuscript. XZ and WH conceptualised and designed the project and supervised the project. W-XM, S-SY and HC performed all the experiments and wrote the manuscript with contributions from all authors. J-MZ revised the manuscript. CZ, L-FH, L-DZ, Y-YF, H-XY and WZ participated in the sample collection and clinical analysis. All authors read and approved the manuscript.

    • Funding This study was supported by grants from the National Natural Science Foundation of China (81325019, 81630044, 81273312, 81601432, 81550023), the National Science Fund for Distinguished Young Scholars of China (813250046), Beijing Municipal Natural Science Foundation (7141008), National Key Research and Development Program: ‘Precise Medical Research’ (2016YFC0903900), CAMS Innovation Fund for Medical Sciences (2016-12M-1-003, 2016-12M-1-008,2017-12M-1-007), and ‘Stem Cell and Translational Research’ (2016YFA0101001).

    • Competing interests None declared.

    • Patient consent Obtained.

    • Ethics approval Institutional Review Board of Peking Union Medical College Hospital.

    • Provenance and peer review Not commissioned; externally peer reviewed.