Anti-CCL22 increases regulatory T cells in CD4+ T cells of rheumatoid arthritis patients via STAT5 pathway

Wang,Ling; Wang,Ling; Hao,Ping; Cao,Qiwei; Zhang,Zhenxian

doi:10.3892/etm.2019.8404

Anti-CCL22 increases regulatory T cells in CD4+ T cells of rheumatoid arthritis patients via STAT5 pathway

Authors:
- Ling Wang
- Ling Wang
- Ping Hao
- Qiwei Cao
- Zhenxian Zhang
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Affiliations: Department of EM, Shuguang Hospital Affiliated to Shanghai University of TCM, Shanghai 200021, P.R. China, Department of Nephrology, Renji Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200001, P.R. China, Department of Orthopedics, Ruijing Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200025, P.R. China, Department of Rheumatism and Immunology, Shanghai Fourth People's Hospital, Shanghai 200081, P.R. China, Traditional Chinese Medicine and Preventive Treatment Center, Yueyang Hospital Affiliated to Shanghai University of TCM, Shanghai 200437, P.R. China
Published online on: December 31, 2019 https://doi.org/10.3892/etm.2019.8404
Pages: 2127-2132
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Abnormality in the number and function of CD4+CD25+FOXP3+ regulatory T cells (Tregs) in peripheral blood has been linked to the initiation and progression of rheumatoid arthritis (RA). Effect of chemokine CCL22 on the number of Tregs in CD4+ T cells and the underlying mechanism were investigated. Downregulation of peripheral Tregs were observed while upregulation of serum chemokine CCL22 in RA patients. Tregs count and the expression of FOXP3 (Tregs function‑related maker) and phosphorylated-signal transducer and activator of transcription 5 (p‑STAT5) in CD4+ T cells from RA patients were increased while C‑C chemokine receptor 4 (CCR4) was decreased by anti‑CCL22 antibody, however, recombinant CCL22 resulted in the opposite effects in CD4+ T cells from the healthy control. STAT5 inhibitor significantly reversed the effects of anti‑CCL22 antibody. Similarly, sinomenine, an anti‑arthritis drug, which decreased CCL22 and CCR4, showed the same trends as the above events, and was reversed by recombinant CCL22 or STAT5 inhibitor. Collectively, anti‑CCL22 induced the number of Tregs via STAT5 pathway, leading to expansion of Tregs and subsequently to control of the autoimmune reaction in RA patients. Our study provides s novel strategy for RA treatment.

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