Zhongde Ye, Timothy M Gould, Huimin Zhang, Jun Jin, Cornelia M Weyand, Jörg J Goronzy
{"title":"GSK3β-β-catenin-TCF1通路通过上调miR-181a改善老年人初始T细胞活化。","authors":"Zhongde Ye, Timothy M Gould, Huimin Zhang, Jun Jin, Cornelia M Weyand, Jörg J Goronzy","doi":"10.1038/s41514-021-00056-9","DOIUrl":null,"url":null,"abstract":"<p><p>MicroRNAs play an important role in the regulation of T cell development, activation, and differentiation. One of the most abundant microRNAs in lymphocytes is miR-181a, which controls T cell receptor (TCR) activation thresholds in thymic selection as well as in peripheral T cell responses. We previously found that miR-181a levels decline in T cells in the elderly. In this study, we identified TCF1 as a transcriptional regulator of pri-miR-181a. A decline in TCF1 levels in old individuals accounted for the reduced miR-181a expression impairing TCR signaling. Inhibition of GSK3ß restored expression of miR-181a by inducing TCF1 in T cells from old adults. GSK3ß inhibition enhanced TCR signaling to increase downstream expression of activation markers and production of IL-2. The effect involved the upregulation of miR-181a and the inhibition of DUSP6 expression. Thus, inhibition of GSK3ß can restore responses of old T cells by inducing miR-181a expression through TCF1.</p>","PeriodicalId":5,"journal":{"name":"ACS Applied Materials & Interfaces","volume":" ","pages":"4"},"PeriodicalIF":8.3000,"publicationDate":"2021-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/s41514-021-00056-9","citationCount":"6","resultStr":"{\"title\":\"The GSK3β-β-catenin-TCF1 pathway improves naive T cell activation in old adults by upregulating miR-181a.\",\"authors\":\"Zhongde Ye, Timothy M Gould, Huimin Zhang, Jun Jin, Cornelia M Weyand, Jörg J Goronzy\",\"doi\":\"10.1038/s41514-021-00056-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>MicroRNAs play an important role in the regulation of T cell development, activation, and differentiation. One of the most abundant microRNAs in lymphocytes is miR-181a, which controls T cell receptor (TCR) activation thresholds in thymic selection as well as in peripheral T cell responses. We previously found that miR-181a levels decline in T cells in the elderly. In this study, we identified TCF1 as a transcriptional regulator of pri-miR-181a. A decline in TCF1 levels in old individuals accounted for the reduced miR-181a expression impairing TCR signaling. Inhibition of GSK3ß restored expression of miR-181a by inducing TCF1 in T cells from old adults. GSK3ß inhibition enhanced TCR signaling to increase downstream expression of activation markers and production of IL-2. The effect involved the upregulation of miR-181a and the inhibition of DUSP6 expression. Thus, inhibition of GSK3ß can restore responses of old T cells by inducing miR-181a expression through TCF1.</p>\",\"PeriodicalId\":5,\"journal\":{\"name\":\"ACS Applied Materials & Interfaces\",\"volume\":\" \",\"pages\":\"4\"},\"PeriodicalIF\":8.3000,\"publicationDate\":\"2021-02-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1038/s41514-021-00056-9\",\"citationCount\":\"6\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Applied Materials & Interfaces\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1038/s41514-021-00056-9\",\"RegionNum\":2,\"RegionCategory\":\"材料科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MATERIALS SCIENCE, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Materials & Interfaces","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1038/s41514-021-00056-9","RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MATERIALS SCIENCE, MULTIDISCIPLINARY","Score":null,"Total":0}
The GSK3β-β-catenin-TCF1 pathway improves naive T cell activation in old adults by upregulating miR-181a.
MicroRNAs play an important role in the regulation of T cell development, activation, and differentiation. One of the most abundant microRNAs in lymphocytes is miR-181a, which controls T cell receptor (TCR) activation thresholds in thymic selection as well as in peripheral T cell responses. We previously found that miR-181a levels decline in T cells in the elderly. In this study, we identified TCF1 as a transcriptional regulator of pri-miR-181a. A decline in TCF1 levels in old individuals accounted for the reduced miR-181a expression impairing TCR signaling. Inhibition of GSK3ß restored expression of miR-181a by inducing TCF1 in T cells from old adults. GSK3ß inhibition enhanced TCR signaling to increase downstream expression of activation markers and production of IL-2. The effect involved the upregulation of miR-181a and the inhibition of DUSP6 expression. Thus, inhibition of GSK3ß can restore responses of old T cells by inducing miR-181a expression through TCF1.
期刊介绍:
ACS Applied Materials & Interfaces is a leading interdisciplinary journal that brings together chemists, engineers, physicists, and biologists to explore the development and utilization of newly-discovered materials and interfacial processes for specific applications. Our journal has experienced remarkable growth since its establishment in 2009, both in terms of the number of articles published and the impact of the research showcased. We are proud to foster a truly global community, with the majority of published articles originating from outside the United States, reflecting the rapid growth of applied research worldwide.