{"title":"在败血症诱导的急性肺损伤中,CircFLNA/miR-214通过调节PD-1来调节调节性T细胞。","authors":"Jian Zhong, Wei Zhang, Leiyun Zhang, Jieying Li, Lingkai Kang, Xiaoyue Li","doi":"10.1080/08916934.2023.2259131","DOIUrl":null,"url":null,"abstract":"<p><p>Sepsis-induced acute respiratory distress syndrome (ARDS) remains a major complication of death from bacterial infection. Regulatory T cells (Tregs) are important regulators in addressing lung injury. Considering the extensive research of circular RNAs (circRNAs), the role of circRNA in Treg modulation during ARDS remains unclear. In this study, patients with sepsis-induced ARDS along with non-ARDS controls were obtained, and bronchoalveolar lavage fluid (BALF) was collected as clinical samples. Additionally, cecal ligation and puncture (CLP) was performed to construct a septic ARDS model, and lung tissues as well as peripheral blood were collected. mRNA expressions were measured by RT-qPCR. ELISA was carried out to measure the concentration of inflammatory factors. A combination of online bioinformatics, dual-luciferase reporter, and RND pull-down assays was performed to verify interactions between microRNA (miRNA) and circRNA/mRNA. Tregs were measured by flow cytometry. Our data suggested that circFLNA was aberrantly elevated in ARDS, and depletion of circFLNA upregulated CD4<sup>+</sup>CD25<sup>+</sup>Foxp3<sup>+</sup> Tregs and decreased inflammatory response. Additionally, miR-214-5p which binds with circFLNA, reversed circFLNA-induced effects in ARDS. Programmed cell death protein 1 (PD-1) is a downstream target gene of miR-214-5p, and abrogated the effects of miR-214-5p on regulating CD4<sup>+</sup>CD25<sup>+</sup>Foxp3<sub>+</sub> Tregs and inflammatory response. In a word, circFLNA/miR-214-5p/PD-1 signaling is a novel pathway that modulates Tregs in ARDS.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":"56 1","pages":"2259131"},"PeriodicalIF":3.3000,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"CircFLNA/miR-214 modulates regulatory T cells by regulating PD-1 in acute lung injury induced by sepsis.\",\"authors\":\"Jian Zhong, Wei Zhang, Leiyun Zhang, Jieying Li, Lingkai Kang, Xiaoyue Li\",\"doi\":\"10.1080/08916934.2023.2259131\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Sepsis-induced acute respiratory distress syndrome (ARDS) remains a major complication of death from bacterial infection. Regulatory T cells (Tregs) are important regulators in addressing lung injury. Considering the extensive research of circular RNAs (circRNAs), the role of circRNA in Treg modulation during ARDS remains unclear. In this study, patients with sepsis-induced ARDS along with non-ARDS controls were obtained, and bronchoalveolar lavage fluid (BALF) was collected as clinical samples. Additionally, cecal ligation and puncture (CLP) was performed to construct a septic ARDS model, and lung tissues as well as peripheral blood were collected. mRNA expressions were measured by RT-qPCR. ELISA was carried out to measure the concentration of inflammatory factors. A combination of online bioinformatics, dual-luciferase reporter, and RND pull-down assays was performed to verify interactions between microRNA (miRNA) and circRNA/mRNA. Tregs were measured by flow cytometry. Our data suggested that circFLNA was aberrantly elevated in ARDS, and depletion of circFLNA upregulated CD4<sup>+</sup>CD25<sup>+</sup>Foxp3<sup>+</sup> Tregs and decreased inflammatory response. Additionally, miR-214-5p which binds with circFLNA, reversed circFLNA-induced effects in ARDS. Programmed cell death protein 1 (PD-1) is a downstream target gene of miR-214-5p, and abrogated the effects of miR-214-5p on regulating CD4<sup>+</sup>CD25<sup>+</sup>Foxp3<sub>+</sub> Tregs and inflammatory response. In a word, circFLNA/miR-214-5p/PD-1 signaling is a novel pathway that modulates Tregs in ARDS.</p>\",\"PeriodicalId\":8688,\"journal\":{\"name\":\"Autoimmunity\",\"volume\":\"56 1\",\"pages\":\"2259131\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2023-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Autoimmunity\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/08916934.2023.2259131\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/9/19 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Autoimmunity","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/08916934.2023.2259131","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/9/19 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
CircFLNA/miR-214 modulates regulatory T cells by regulating PD-1 in acute lung injury induced by sepsis.
Sepsis-induced acute respiratory distress syndrome (ARDS) remains a major complication of death from bacterial infection. Regulatory T cells (Tregs) are important regulators in addressing lung injury. Considering the extensive research of circular RNAs (circRNAs), the role of circRNA in Treg modulation during ARDS remains unclear. In this study, patients with sepsis-induced ARDS along with non-ARDS controls were obtained, and bronchoalveolar lavage fluid (BALF) was collected as clinical samples. Additionally, cecal ligation and puncture (CLP) was performed to construct a septic ARDS model, and lung tissues as well as peripheral blood were collected. mRNA expressions were measured by RT-qPCR. ELISA was carried out to measure the concentration of inflammatory factors. A combination of online bioinformatics, dual-luciferase reporter, and RND pull-down assays was performed to verify interactions between microRNA (miRNA) and circRNA/mRNA. Tregs were measured by flow cytometry. Our data suggested that circFLNA was aberrantly elevated in ARDS, and depletion of circFLNA upregulated CD4+CD25+Foxp3+ Tregs and decreased inflammatory response. Additionally, miR-214-5p which binds with circFLNA, reversed circFLNA-induced effects in ARDS. Programmed cell death protein 1 (PD-1) is a downstream target gene of miR-214-5p, and abrogated the effects of miR-214-5p on regulating CD4+CD25+Foxp3+ Tregs and inflammatory response. In a word, circFLNA/miR-214-5p/PD-1 signaling is a novel pathway that modulates Tregs in ARDS.
期刊介绍:
Autoimmunity is an international, peer reviewed journal that publishes articles on cell and molecular immunology, immunogenetics, molecular biology and autoimmunity. Current understanding of immunity and autoimmunity is being furthered by the progress in new molecular sciences that has recently been little short of spectacular. In addition to the basic elements and mechanisms of the immune system, Autoimmunity is interested in the cellular and molecular processes associated with systemic lupus erythematosus, rheumatoid arthritis, Sjogren syndrome, type I diabetes, multiple sclerosis and other systemic and organ-specific autoimmune disorders. The journal reflects the immunology areas where scientific progress is most rapid. It is a valuable tool to basic and translational researchers in cell biology, genetics and molecular biology of immunity and autoimmunity.