Role of Chemotaxis of Vδ2 T Cells to the Synovium in the Pathogenesis of Acute Gouty Arthritis

Hong Di; Xinxin Han; Yue Yin; Yun Zhang; Xuejun Zeng

doi:10.2147/JIR.S449329

Role of Chemotaxis of Vδ2 T Cells to the Synovium in the Pathogenesis of Acute Gouty Arthritis

J Inflamm Res. 2024 Feb 7:17:721-736. doi: 10.2147/JIR.S449329. eCollection 2024.

Authors

Hong Di^#¹, Xinxin Han^#¹, Yue Yin¹, Yun Zhang¹, Xuejun Zeng¹

Affiliation

¹ Department of Family Medicine & Division of General Internal Medicine, Department of Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, State Key Laboratory of Complex Severe and Rare Diseases (Peking Union Medical College Hospital), Beijing, People's Republic of China.

^# Contributed equally.

Abstract

Background: This study aimed to explore the potential roles of Vδ2 T cells in the pathogenesis of acute gouty arthritis.

Methods: Patients with gout (n=86), rheumatoid arthritis (n=7), osteoarthritis (n=9), and healthy controls (n=40) were enrolled. γδT cell frequency, chemokine receptor expression and production of pro-inflammatory cytokines in cells from peripheral blood and synovial fluid samples were quantified by flow cytometry. The chemotaxis ability of Vδ2 T cells was determined by transwell migration assay. The levels of chemokines were also detected by enzyme-linked immunosorbent assay.

Results: Peripheral Vδ2 T cells had significantly lower frequencies in acute gout patients than that in healthy controls (P<0.001). These peripheral Vδ2 T cells were negatively correlated with inflammatory markers. Vδ2 T cells from acute gout patients accumulated in synovial fluid, as evidenced by a higher abundance of Vδ2 T cells in it than that in the serum (P<0.01). And Vδ2 T cells expressed a high level of C-X-C chemokine receptor 3 (P=0.035), and its corresponding chemokine C-X-C motif chemokine ligand 10 showed a high concentration in synovial fluid (P<0.05). Vδ2 T cells from synovial fluid of acute gout patients produced a high level of interleukin-17 (P=0.033).

Conclusion: The up-regulated expression of C-X-C chemokine receptor 3 on Vδ2 T cells potentially facilitates their infiltration into synovial fluid during acute gouty arthritis. Further production of interleukin-17 by Vδ2 T cells may contribute to the pathogenesis of gout. This study sheds new light on developing novel Vδ2 T cells-based therapeutic strategies for gout treatment.

Keywords: CXCL10; CXCR3; Interleukin-17; Vδ2 T cells; acute gouty arthritis; γδT cells.

Grants and funding

This work was supported by the National Natural Science Foundation of China (Grant No. 81901667 and 82071841) and National High Level Hospital Clinical Research Funding (2022-PUMCH-B-044).