The GSK3β-β-catenin-TCF1 pathway improves naive T cell activation in old adults by upregulating miR-181a

Zhongde Ye, Timothy M. Gould, Huimin Zhang, Jun Jin, Cornelia M. Weyand, Jörg J. Goronzy

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Article number4
Journalnpj Aging and Mechanisms of Disease
Volume7
Issue number1
DOIs
StatePublished - Dec 2021

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

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