变应原免疫疗法通过减少PU-1+调节性T细胞数量来增强调节性T细胞的免疫抑制作用，从而减轻过敏性鼻炎。
Allergen immunotherapy enhances the immunosuppressive effects of Treg cells to alleviate allergic rhinitis by decreasing PU-1+ Treg cell numbers.
作者信息
Qiao Yue-Long, Jiao Wo-Er, Xu Shan, Kong Yong-Gang, Deng Yu-Qin, Yang Rui, Hua Qing-Quan, Chen Shi-Ming
机构信息
Department of Otolaryngology-Head and Neck Surgery, Central Laboratory, Renmin Hospital of Wuhan University, 238 Jie-Fang Road, Wuhan, Hubei 430060, PR China.
Department of Otolaryngology-Head and Neck Surgery, Central Laboratory, Renmin Hospital of Wuhan University, 238 Jie-Fang Road, Wuhan, Hubei 430060, PR China.
出版信息
Int Immunopharmacol. 2022 Nov;112:109187. doi: 10.1016/j.intimp.2022.109187. Epub 2022 Aug 26.
OBJECTIVE
To investigate the role of Tregs and their subtypes in the treatment of allergic rhinitis with allergen immunotherapy (AIT) as well as the underlying mechanism.
METHODS
- Thirty-one healthy controls, 29 Allergic rhinitis (AR) patients and 16 AR patients treated with AIT were recruited. The total nasal symptom scores (TNSSs) were calculated. The serum levels of IgE, IL-2, TNF-α, IFN-γ, IL-4, IL-5, IL-6, IL-10 and IL-17 were measured. 2. Changes in the proportions of CD4+ T cells, Treg cells, Treg subtypes and Th1/Th2/Th9/Th17/Tfh cells in the peripheral blood of the subjects in the three groups were measured. 3. The correlations of Treg cells, Treg subtypes and TNSS with the levels of various cytokines in the AR group and AIT group were analysed.
RESULTS
- Compared with the control group, the TNSS and IgE, IL-5 and IL-6 levels in the AR group were significantly increased, while the IL-2, IFN-γ and IL-10 levels were significantly decreased (P < 0.05). Compared with the AR group, the TNSS and IgE, IL-5 and IL-6 levels in the AIT group were significantly decreased, while the IL-2, IFN-γ and IL-10 levels were significantly increased (P < 0.05). 2. Compared with the control group, the proportions of Tregs, GATA3+ Tregs and Th1 cells in the AR group were significantly reduced, while the proportions of PU-1+ Tregs, T-bet+ Tregs and Th2 cells were significantly increased (P < 0.05). Compared with the AR group, the proportions of Tregs and Th1 cells in the AIT group were significantly increased, while the proportions of PU-1+ Tregs and Th2 cells were decreased (P < 0.05). 3. Correlation analysis showed that Treg cell proportions were negatively correlated with the TNSS, sIgE levels, IL-5 levels and IL-6 levels but positively correlated with the IL-2 and IL-10 levels (P < 0.05). PU-1+ Treg cell proportions were positively correlated with the TNSS, sIgE levels, IL-5 levels and IL-6 levels but negatively correlated with the Treg cell proportions, IL-2 levels and IL-10 levels (P < 0.05).
CONCLUSIONS
AIT can reduce the proportions of PU-1+ Treg subtypes in AR patients. PU-1+ Treg cell numbers can potentially be used as an indicator to monitor the therapeutic effect of AIT on AR.
目的
探讨调节性T细胞（Tregs）及其亚型在变应原免疫治疗（AIT）治疗变应性鼻炎中的作用及其潜在机制。
方法
- 招募31名健康对照者、29名变应性鼻炎（AR）患者和16名接受AIT治疗的AR患者。计算总鼻症状评分（TNSSs）。检测血清免疫球蛋白E（IgE）、白细胞介素-2（IL-2）、肿瘤坏死因子-α（TNF-α）、干扰素-γ（IFN-γ）、白细胞介素-4（IL-4）、白细胞介素-5（IL-5）、白细胞介素-6（IL-6）、白细胞介素-10（IL-10）和白细胞介素-17（IL-17）水平。2. 检测三组受试者外周血中CD4⁺ T细胞、Tregs细胞、Tregs亚型及辅助性T细胞1/辅助性T细胞2/辅助性T细胞9/辅助性T细胞17/滤泡辅助性T细胞（Th1/Th2/Th9/Th17/Tfh）细胞比例的变化。3. 分析AR组和AIT组中Tregs细胞、Tregs亚型及TNSS与各种细胞因子水平的相关性。
结果
- 与对照组相比，AR组的TNSS以及IgE、IL-5和IL-6水平显著升高，而IL-2、IFN-γ和IL-10水平显著降低（P<0.05）。与AR组相比，AIT组的TNSS以及IgE、IL-5和IL-6水平显著降低，而IL-2、IFN-γ和IL-10水平显著升高（P<0.05）。2. 与对照组相比，AR组中Tregs细胞、GATA3⁺ Tregs细胞和Th1细胞的比例显著降低，而PU-1⁺ Tregs细胞、T-bet⁺ Tregs细胞和Th2细胞的比例显著升高（P<0.05）。与AR组相比，AIT组中Tregs细胞和Th1细胞的比例显著升高，而PU-1⁺ Tregs细胞和Th2细胞的比例降低（P<0.05）。3. 相关性分析显示，Tregs细胞比例与TNSS、特异性IgE（sIgE）水平、IL-5水平和IL-6水平呈负相关，但与IL-2和IL-10水平呈正相关（P<0.05）。PU-1⁺ Tregs细胞比例与TNSS、sIgE水平、IL-5水平和IL-6水平呈正相关，但与Tregs细胞比例、IL-2水平和IL-10水平呈负相关（P<0.05）。
结论
AIT可降低AR患者中PU-1⁺ Tregs亚型的比例。PU-1⁺ Tregs细胞数量有可能作为监测AIT治疗AR疗效的指标。
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