髓源性抑制细胞通过调节Th1/Th2/Th17反应加重儿童和卵清蛋白过敏小鼠的哮喘进展。
MDSCs Aggravate the Asthmatic Progression in Children and OVA-Allergic Mice by Regulating the Th1/Th2/Th17 Responses.
作者信息
Lin Long, Xu Shifu, Peng Feng, Jin Haili, Xiao Fengchun
机构信息
Department of Pediatrics, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Department of Pathology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310016, China.
出版信息
Evid Based Complement Alternat Med. 2022 Aug 22;2022:6157385. doi: 10.1155/2022/6157385. eCollection 2022.
BACKGROUND
Asthma is a chronic inflammatory disease of respiratory with serious risks for children. This study explored myeloid-derived suppressor cells (MDSCs) on the pathogenesis of asthmatic children and mice.
METHODS
The clinical study enrolled 30 asthma, 20 pneumonia, and 20 control participants. The MDSCs, Th17 and Th1 cells percentage, and IL-4, IL-12, IL-10, and IFN- levels were detected by flow cytometry and ELISA. In experimental asthma, mice were divided into control, ovalbumin (OVA), and OVA + MDSCs groups. The changes in inflammatory cell count and the levels of IL-5, IL-12, and IL-10 in mice BALF and the levels of inflammatory factors, IgE, and IFN- in mice were detected by ELISA. The amount of ROS generation and pathological changes and the levels of caspase 1 and caspase 3 were tested by flow cytometry, HE and PAS staining, and immunohistochemistry. The expression of cleaved caspase 1/caspase 1 and cleaved caspase 3/caspase 3 was detected by western blot.
RESULTS
In clinical trials, the levels of IL-12, IFN-, and Th1 percentage decreased in pneumonia and asthma children's peripheral blood, while the levels of IL-4 and IL-10 and the percentages MDSCs and Th17 increased. In asthma mice, pathological staining showed that asthma caused lung inflammation and damage, while the OVA + MDSC group was severer. Moreover, the percentages of eosinophils, neutrophils, lymphocytes, and the levels of inflammatory factors, IgE, ROS production, caspase 1, caspase 3, cleaved caspase 1/caspase 1, and cleaved caspase 3/caspase 3 increased in OVA + MDSC group, while the percentage of macrophages, IL-12, and IFN- levels reduced, illustrating that MDSCs exacerbated asthma.
CONCLUSION
Our study indicated that MDSCs could aggravate asthma by regulating the Th1/Th2/Th17 response.
背景
哮喘是一种慢性呼吸道炎症性疾病，对儿童有严重风险。本研究探讨了髓源性抑制细胞（MDSCs）在哮喘儿童及小鼠发病机制中的作用。
方法
临床研究纳入30例哮喘患儿、20例肺炎患儿及20例对照参与者。采用流式细胞术和酶联免疫吸附测定（ELISA）检测MDSCs、Th17和Th1细胞百分比以及白细胞介素-4（IL-4）、白细胞介素-12（IL-12）、白细胞介素-10（IL-10）和干扰素（IFN）水平。在实验性哮喘中，将小鼠分为对照组、卵清蛋白（OVA）组和OVA + MDSCs组。采用ELISA检测小鼠支气管肺泡灌洗液（BALF）中炎症细胞计数及IL-5、IL-12和IL-10水平，以及小鼠体内炎症因子、免疫球蛋白E（IgE）和IFN水平。通过流式细胞术、苏木精-伊红（HE）和过碘酸-雪夫（PAS）染色以及免疫组织化学检测活性氧（ROS）生成量、病理变化以及半胱天冬酶1（caspase 1）和半胱天冬酶3（caspase 3）水平。采用蛋白质免疫印迹法检测裂解的caspase 1/caspase 1和裂解的caspase 3/caspase 3的表达。
结果
在临床试验中，肺炎和哮喘患儿外周血中IL-12、IFN水平及Th1百分比降低，而IL-4和IL-10水平以及MDSCs和Th17百分比升高。在哮喘小鼠中，病理染色显示哮喘导致肺部炎症和损伤，而OVA + MDSCs组更严重。此外，OVA + MDSCs组中嗜酸性粒细胞、中性粒细胞、淋巴细胞百分比以及炎症因子、IgE、ROS生成量、caspase 1、caspase 3、裂解的caspase 1/caspase 1和裂解的caspase 3/caspase 3水平升高，而巨噬细胞百分比、IL-12和IFN水平降低，说明MDSCs加剧了哮喘。
结论
我们的研究表明，MDSCs可通过调节Th1/Th2/Th17反应加重哮喘。
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