The GSK3β-β-catenin-TCF1 pathway improves naive T cell activation in old adults by upregulating miR-181a
Abstract 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....
Guardado en:
| Autores principales: | , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Nature Portfolio
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/08e6f57628f742cbbf6c188b84d4f6a7 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:08e6f57628f742cbbf6c188b84d4f6a7 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:08e6f57628f742cbbf6c188b84d4f6a72021-12-02T13:50:57ZThe GSK3β-β-catenin-TCF1 pathway improves naive T cell activation in old adults by upregulating miR-181a10.1038/s41514-021-00056-92056-3973https://doaj.org/article/08e6f57628f742cbbf6c188b84d4f6a72021-02-01T00:00:00Zhttps://doi.org/10.1038/s41514-021-00056-9https://doaj.org/toc/2056-3973Abstract 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.Zhongde YeTimothy M. GouldHuimin ZhangJun JinCornelia M. WeyandJörg J. GoronzyNature PortfolioarticleGeriatricsRC952-954.6ENnpj Aging and Mechanisms of Disease, Vol 7, Iss 1, Pp 1-9 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Geriatrics RC952-954.6 |
| spellingShingle |
Geriatrics RC952-954.6 Zhongde Ye Timothy M. Gould Huimin Zhang Jun Jin Cornelia M. Weyand Jörg J. Goronzy The GSK3β-β-catenin-TCF1 pathway improves naive T cell activation in old adults by upregulating miR-181a |
| description |
Abstract 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. |
| format |
article |
| author |
Zhongde Ye Timothy M. Gould Huimin Zhang Jun Jin Cornelia M. Weyand Jörg J. Goronzy |
| author_facet |
Zhongde Ye Timothy M. Gould Huimin Zhang Jun Jin Cornelia M. Weyand Jörg J. Goronzy |
| author_sort |
Zhongde Ye |
| title |
The GSK3β-β-catenin-TCF1 pathway improves naive T cell activation in old adults by upregulating miR-181a |
| title_short |
The GSK3β-β-catenin-TCF1 pathway improves naive T cell activation in old adults by upregulating miR-181a |
| title_full |
The GSK3β-β-catenin-TCF1 pathway improves naive T cell activation in old adults by upregulating miR-181a |
| title_fullStr |
The GSK3β-β-catenin-TCF1 pathway improves naive T cell activation in old adults by upregulating miR-181a |
| title_full_unstemmed |
The GSK3β-β-catenin-TCF1 pathway improves naive T cell activation in old adults by upregulating miR-181a |
| title_sort |
gsk3β-β-catenin-tcf1 pathway improves naive t cell activation in old adults by upregulating mir-181a |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/08e6f57628f742cbbf6c188b84d4f6a7 |
| work_keys_str_mv |
AT zhongdeye thegsk3bbcatenintcf1pathwayimprovesnaivetcellactivationinoldadultsbyupregulatingmir181a AT timothymgould thegsk3bbcatenintcf1pathwayimprovesnaivetcellactivationinoldadultsbyupregulatingmir181a AT huiminzhang thegsk3bbcatenintcf1pathwayimprovesnaivetcellactivationinoldadultsbyupregulatingmir181a AT junjin thegsk3bbcatenintcf1pathwayimprovesnaivetcellactivationinoldadultsbyupregulatingmir181a AT corneliamweyand thegsk3bbcatenintcf1pathwayimprovesnaivetcellactivationinoldadultsbyupregulatingmir181a AT jorgjgoronzy thegsk3bbcatenintcf1pathwayimprovesnaivetcellactivationinoldadultsbyupregulatingmir181a AT zhongdeye gsk3bbcatenintcf1pathwayimprovesnaivetcellactivationinoldadultsbyupregulatingmir181a AT timothymgould gsk3bbcatenintcf1pathwayimprovesnaivetcellactivationinoldadultsbyupregulatingmir181a AT huiminzhang gsk3bbcatenintcf1pathwayimprovesnaivetcellactivationinoldadultsbyupregulatingmir181a AT junjin gsk3bbcatenintcf1pathwayimprovesnaivetcellactivationinoldadultsbyupregulatingmir181a AT corneliamweyand gsk3bbcatenintcf1pathwayimprovesnaivetcellactivationinoldadultsbyupregulatingmir181a AT jorgjgoronzy gsk3bbcatenintcf1pathwayimprovesnaivetcellactivationinoldadultsbyupregulatingmir181a |
| _version_ |
1718392418797092864 |