The influence of interleukin-35 on the balance between regulatory T cells and T helper 22 cells in patients with Hashimoto′s thyroiditis
10.3760/cma.j.cn311282-20240201-00052
- VernacularTitle:白细胞介素-35对桥本甲状腺炎患者调节性T细胞和辅助性T细胞22平衡的影响
- Author:
Lichao ZHAO
1
;
Jianlin ZHAO
;
Huifang CAO
;
Jiangyan LI
;
Yanhong ZHOU
Author Information
1. 新乡市中心医院（新乡医学院第四临床学院）内分泌科，新乡 453000
- Keywords:
Hashimoto′s thyroiditis;
Interleukin-35;
Regulatory T cells;
T helper 22 cells
- From:
Chinese Journal of Endocrinology and Metabolism
2024;40(8):669-675
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To observe the expression of interleukin-35(IL-35) in Hashimoto's thyroiditis(HT) patients, and evaluate its regulatory effect on the balance between regulatory T cells(Treg) and T helper 22(Th22) cells.Methods:Forty-two HT patients and eighteen controls were consecutively enrolled. Plasma and peripheral blood mononuclear cells(PBMC) were isolated. Treg were purified. Plasma IL-35 and IL-22 were detected with enzyme-linked immunosorbent assay. Treg and Th22 percentages were measured using flow cytometry. Real-time quantitative PCR was used to assess mRNA levels of forhead box protein 3(FoxP3) and aryl hydrocarbon receptor(AhR). Treg were stimulated with exogenous IL-35, and were co-cultured with autologous PBMC to induce Treg-to-Th22 phenotypic differentiation, evaluating the effect of IL-35 on Treg function and differentiation.Results:There was imbalance between Treg and Th22 cells in HT group. HT group had reduced Treg percentage, plasma IL-35 and FoxP3 mRNA( P<0.001), while had elevated Th22 percentage and AhR mRNA( P<0.001). There was no significant difference in plasma IL-22 level between two groups( P=0.775). The suppressive capacity of Tregs in the HT group was diminished( P=0.013), and secretion levels of IL-35 and IL-10 were lower than those in the control group( P<0.001). The ability of Tregs in the HT group to differentiate into Th22 cells was increased, with higher levels of CCR4, CCR6, CCR10, AhR mRNA, and IL-22 secretion compared to the control group( P<0.01). IL-35 stimulation induced elevation of Treg percentage, FoxP3 mRNA, and IL-35/IL-10 secretion( P<0.05), but did not affect Th22 percentage, AhR mRNA, or IL-22 secretion( P>0.05). IL-35 stimulation enhanced Treg function in HT group, increasing proliferation inhibition and secretion of IL-35 and IL-10( P<0.05). IL-35 stimulation reduced the differentiation of Treg to Th22 phenotype in HT group, with decreased levels of CCR4, CCR6 CCR10, AhR mRNA, and IL-22 secretion( P<0.05). Conclusion:IL-35 enhances the immunosuppression of Tregs in HT patients and inhibits its differentiation into Th22 cells, thus regulating the balance between Tregs and Th22 cells.
