Department of Emergency, Anhui Children's Hospital, 39 Wangjiang East Road, Baohe District, Hefei 230051, China; Department of Emergency, Anhui Medical University Affiliated Provincial Children's Hospital, Hefei 230051, China.
Department of Emergency, Anhui Children's Hospital, 39 Wangjiang East Road, Baohe District, Hefei 230051, China.
Hum Immunol. 2021 Oct;82(10):775-781. doi: 10.1016/j.humimm.2021.07.002. Epub 2021 Jul 20.
Th9 is a subset of CD4 T cells that mainly secrete IL-9. Th9/IL-9 participates in immune response during Staphylococcus aureus and methicillin-resistant Staphylococcus aureus pneumonia (MRSA) infection. Here, we collected bronchoalveolar lavage fluid (BALF) from 30 children with MRSA pneumonia (MRSA group) and 10 children with bronchial foreign bodies (Control group). RT-PCR, ELISA and flow cytometry were used to detect the expression of miR-155 and IL-9 in BALF and the number of Th9 cells. CD4 T cells isolated from BALF of MRSA and Control group were transfected with miR-155 mimic or inhibitor, and then induced Th9 cell differentiation. The results showed that the expression of miR-155 and IL-9 were significantly increased in BALF and Th9 cell of MRSA group, as well as the number of Th9 cells. miR-155 mimic upregulated IL-9 mRNA expression, IL-9 secretion and increased number of Th9 cells. On the contrary, miR-155 inhibitor inhibited IL-9 mRNA expression, IL-9 secretion and decreased number of Th9 cells. The dual luciferase assays demonstrated miR-155 can target binding to SIRT1 3'UTR. Moreover, overexpression of SIRT1 could reverse the effect of miR-155 mimic on IL-9 expression level, Th9 cell number and transcription factors PU.1 and IRF4 expression. In conclusion, miR-155 regulates Th9 differentiation in children with MRSA by targeting SIRT1.
Th9 是 CD4 T 细胞的一个亚群，主要分泌 IL-9。Th9/IL-9 参与金黄色葡萄球菌和耐甲氧西林金黄色葡萄球菌肺炎（MRSA）感染期间的免疫反应。在这里，我们收集了 30 例 MRSA 肺炎患儿（MRSA 组）和 10 例支气管异物患儿（对照组）的支气管肺泡灌洗液（BALF）。采用 RT-PCR、ELISA 和流式细胞术检测 BALF 中 miR-155 和 IL-9 的表达以及 Th9 细胞的数量。从 MRSA 和对照组 BALF 中分离出 CD4 T 细胞，用 miR-155 模拟物或抑制剂转染，然后诱导 Th9 细胞分化。结果表明，MRSA 组 BALF 和 Th9 细胞中 miR-155 和 IL-9 的表达明显增加，Th9 细胞的数量也增加。miR-155 模拟物上调 IL-9 mRNA 表达、IL-9 分泌和 Th9 细胞数量。相反，miR-155 抑制剂抑制 IL-9 mRNA 表达、IL-9 分泌和 Th9 细胞数量减少。双荧光素酶报告基因实验证实 miR-155 可以靶向结合 SIRT1 3'UTR。此外，SIRT1 的过表达可以逆转 miR-155 模拟物对 IL-9 表达水平、Th9 细胞数量和转录因子 PU.1 和 IRF4 表达的影响。总之，miR-155 通过靶向 SIRT1 调节儿童 MRSA 中的 Th9 分化。
