Aberrant Th2 Immune Responses Are Associated With a Reduced Frequency of IL-35-Induced Regulatory T Cells After Allergen Exposure in Patients With Allergic Asthma
Aberrant Th2 Immune Responses Are Associated With a Reduced Frequency of IL-35-Induced Regulatory T Cells After Allergen Exposure in Patients With Allergic Asthma
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过敏性哮喘患者接触过敏原后，异常的 Th2 免疫反应与 IL-35 诱导的调节性 T 细胞频率降低相关
DOI：
10.4168/aair.2020.12.6.1029
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发表时间：
2020-11-01
影响因子：
4.4
通讯作者：
Yang, Jiong
中科院分区：
文献类型：
--
作者：
Wang, Wei;Wei, Chaojie;Yang, Jiong
目的过敏原暴露可诱导过敏性哮喘患者T辅助细胞(Th)2的异常免疫反应，但对致敏、无症状和非过敏者无明显影响。白细胞介素35(IL-35)诱导的调节性T细胞(ITr35)是具有免疫调节功能的调节性T细胞的新亚群。这些细胞可以显著抑制季节性变应性鼻炎患者的Th2反应。然而，目前尚不清楚iTr35细胞是否参与了特定过敏原暴露后过敏性哮喘患者的免疫调节。方法检测过敏性哮喘患者、无症状哮喘患者和健康体检者外周血单个核细胞(PBMC)中iTr35细胞频率。此外，我们还研究了变应原刺激下，幼稚的CD4+T细胞在体外转化为iTr35细胞的差异。体外研究iTr35细胞对初始CD_4~+T细胞向Th2细胞分化、CD_4+CD_(25)−T细胞增殖和Th2细胞因子产生的影响。结果与无症状组和正常对照组比较，哮喘合并皮肤病变态反应组iTr35细胞频率和IL-35表达水平显著降低。哮喘患者外周血中iTr35细胞比例和IL-35表达水平随病情加重而逐渐降低。与无症状的健康受试者相比，过敏性哮喘患者暴露后幼稚的CD4+T细胞向iTr35细胞的转化和IL-35的产生减少。最重要的是，iTr35细胞以IL-35依赖的方式抑制变应原诱导的初始CD4+T细胞向Th2细胞的分化、TJeff细胞的增殖和Th2细胞因子的产生。结论iTr35细胞可能通过分泌IL-35在阻止Th2细胞对变应原的反应中发挥重要作用，iTr35细胞可能是治疗过敏性哮喘的一种新的免疫调节剂。
Purpose Allergen exposure induces aberrant T helper (Th) 2 immune responses in patients with allergic asthma, but not in sensitized asymptomatic and nonallergic subjects. Interleukin (IL)-35-induced regulatory T (iTr35) cells are a new subset of regulatory T cells with immunoregulatory properties. These cells can significantly suppress Th2 responses in seasonal allergic rhinitis. However, it remains unknown whether iTr35 cells are involved in the immunoregulation of allergic asthmatic individuals after specific allergen exposure. Methods The iTr35 cell frequency in peripheral blood mononuclear cells (PBMCs) was measured in patients with allergic asthma as well as in asymptomatic and healthy subjects. The difference in naïve CD4+ T cell conversion to iTr35 cells in vitro during allergen stimulation was also investigated. The effects of iTr35 cells on naïve CD4+ T cell differentiation into Th2 cells, CD4+CD25− T (Teff) cell proliferation and Th2 cytokine production in vitro were assessed. Results Significantly reduced iTr35 cell frequencies and IL-35 expression levels were found in asthmatic patients with Derp1 allergy compared with asymptomatic and healthy subjects. Moreover, the circulating iTr35 cell proportion and IL-35 expression level in asthmatic patients gradually decreased with disease severity. Patients with allergic asthma had reduced transformation of naïve CD4+ T cells into iTr35 cells and IL-35 production after allergen exposure compared with asymptomatic and healthy subjects. Most importantly, iTr35 cells inhibited allergen-driven differentiation of naïve CD4+ T cells into Th2 cells, Teff cell proliferation and Th2 cytokine production in an IL-35-dependent manner. Conclusions The results of our study suggest that iTr35 cells may play an important role in preventing Th2 responses to allergens by secreting IL-35 and that iTr35 cells may be a potential new immune regulator of allergic asthma.