The GSK3β-β-catenin-TCF1 Pathway Improves Naive T Cell Activation in Old Adults by Upregulating MiR-181a

Overview

Journal NPJ Aging Mech Dis

Specialty Geriatrics

Date 2021 Feb 9

PMID 33558531

Citations 7

Authors

Zhongde Ye

Timothy M Gould

Huimin Zhang

Jun Jin

Cornelia M Weyand

Jorg J Goronzy

Affiliations

Soon will be listed here.

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.

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