Guo Rong-Hong, Cheng Hao, Zhang Xiao-Ying, Yu Zhen, Wang Guang-Hui, Hao Shu-Ya, Gao Xiao-Peng, Wen Hong-Yan
Department of Rheumatology, Shanxi Medical University, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
Front Pharmacol. 2022 Nov 3;13:986199. doi: 10.3389/fphar.2022.986199. eCollection 2022.
T cells represent a predominant cell type in autoimmune disease. However, their exact roles are not fully clear in systemic sclerosis (SSc). This study aimed to mainly investigate the alteration in the absolute numbers of T-lymphocyte subsets and the serum levels of cytokines in SSc patients. A total of 76 patients with SSc and 76 age- and sex-matched healthy controls (HCs) were enrolled. The levels of circulating T cell subsets and serum cytokines were measured by flow cytometry. T cell subsets or serum cytokines correlations with disease activity and organ involvement were analyzed. The absolute numbers of Th2 and Treg cells in SSc patients were lower than those in HCs ( < 0.05), resulting in the ratios of Th1/Th2 [25.01 (12.24, 38.61) vs. 11.64 (6.38, 20.34)] and Th17/Treg [0.42 (0.17, 0.66) vs. 0.17 (0.13, 0.29)] were increased significantly ( < 0.001). The absolute numbers of total T, Th, and Treg cells were negatively correlated with CRP ( = -0.406, = 0.002; = -0.263, < 0.05; = -0.367 < 0.01). The serum levels of IL-2, SIL-2R, IL-6, IL-10, INF-γ, and TNF-α were significantly higher than those in HCs ( < 0.001). Increasing IL-2 in the wake of the augment of ESR ( = 0.671, = 0.004), so did IL-6 ( = 0.378, < 0.05). The ratio of Th17/Treg in SSc-ILD patients had lower levels than that in other patients [0.35 (0.14, 0.53) vs. 0.64 (0.26, 0.93) = 0.028]; Treg cells were lessened in patients with Raynaud's phenomenon relative to controls [3.00 (2.41, 4.28) vs. 3.55 (2.86, 4.53) < 0.05]. The levels of IL-2, IL-10 and INF-γ [3.32 (1.05,11.73) vs. 2.32 (0.44,6.45), = 0.045], [8.08 (3.63, 355,77) vs. 4.89 (0.78, 21.44), = 0.02], [6.31 (2.66, 44.03) vs. 4.03 (0.22, 16.96), = 0.009] were elevated in patients with arthralgia, while the level of Th17 was decreased [0.62 (0.20,2.16) vs. 1.26 (0.22,10.93), = 0.026]. ROC curve analysis yielded an optimal cut-off IL-2, IL-10, and INF-γ levels of 2.67, 5.93, and 5.32 pg/ml for the presence of arthralgia. We exhibited abnormalities in T subsets and the production of their cytokines in SSc, as compared with those in HCs. This may allow the pathogenesis of SSc and the development of novel therapeutic interventions aimed at targeting these cells and the cytokines they produce.
T细胞是自身免疫性疾病中的主要细胞类型。然而，它们在系统性硬化症（SSc）中的确切作用尚不完全清楚。本研究旨在主要调查SSc患者T淋巴细胞亚群的绝对数量变化以及细胞因子的血清水平。共纳入76例SSc患者和76例年龄及性别匹配的健康对照（HC）。通过流式细胞术检测循环T细胞亚群水平和血清细胞因子。分析了T细胞亚群或血清细胞因子与疾病活动度和器官受累情况的相关性。SSc患者中Th2和Treg细胞的绝对数量低于HC（<0.05），导致Th1/Th2比值[25.01（12.24，38.61）对11.64（6.38，20.34）]和Th17/Treg比值[0.42（0.17，0.66）对0.17（0.13，0.29）]显著升高（<0.001）。总T细胞、Th细胞和Treg细胞的绝对数量与CRP呈负相关（r = -0.406，P = 0.002；r = -0.263，P < 0.05；r = -0.367，P < 0.01）。SSc患者血清IL-2、SIL-2R、IL-6、IL-10、INF-γ和TNF-α水平显著高于HC（<0.001）。ESR升高后IL-2增加（r = 0.671，P = 0.004），IL-6也如此（r = 0.378，P < 0.05）。SSc-ILD患者的Th17/Treg比值低于其他患者[0.35（0.14，0.53）对0.64（0.26，0.93），P = 0.028]；相对于对照组，雷诺现象患者的Treg细胞减少[3.00（2.41，4.28）对3.55（2.86，4.53），P < 0.05]。关节痛患者的IL-2、IL-10和INF-γ水平升高[3.32（1.05，11.73）对2.32（0.44，6.45），P = 0.045]，[8.08（3.63，355.77）对4.89（0.78，21.44），P = 0.02]，[6.31（2.66，44.03）对4.03（0.22，16.9,6），P = 0.009]，而Th17水平降低[0.62（0.20，2.16）对1.26（0.22，10.93），P = 0.026]。ROC曲线分析得出关节痛存在时IL-2、IL-10和INF-γ的最佳截断水平分别为2.67、5.93和5.32 pg/ml。与HC相比，我们发现SSc患者的T亚群及其细胞因子产生存在异常。这可能有助于了解SSc的发病机制，并开发针对这些细胞及其产生的细胞因子的新型治疗干预措施。
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