miR-181a-regulated pathways in T-cell differentiation and aging

Chulwoo Kim, Zhongde Ye, Cornelia M. Weyand, Jörg J. Goronzy

    Research output: Contribution to journalReview articlepeer-review

    34 Citations (Scopus)

    Abstract

    MicroRNAs (miRNAs) are regulatory noncoding RNAs important for many aspects of cellular processes including cell differentiation and proliferation. Functions of numerous miRNAs have been identified in T cells, with miR-181a regulating T cell activation thresholds during thymic T cell development and during activation of peripheral T cells. Intriguingly, miR-181a is implicated in defective antiviral and vaccine responses in older individuals, as its expression declines in naïve T cells with increasing age. Here, we review the pathways that are regulated by miR-181a and that explain the unique role of miR-181a in T cell development, T cell activation and antiviral T cell responses. These studies provide a framework for understanding how a decline in miR-181a expression in T cells could contribute to age-related defects in adaptive immunity. We furthermore review the mechanisms that cause the age-related decline in miR-181a expression and discuss the potential of restoring miR-181a expression or targeting miR-181a-regulated pathways to improve impaired T cell responses in older individuals.

    Original languageEnglish
    Article number28
    JournalImmunity and Ageing
    Volume18
    Issue number1
    DOIs
    Publication statusPublished - 2021 Dec

    Bibliographical note

    Funding Information:
    This work was supported by the National Institutes of Health R01 AR042527, R01 HL117913, R01 AI108906, R01 HL142068, and P01 HL129941 to C.M.W., R01 AI108891, R01 AG045779, U19 AI057266 and R01 AI129191 to J.J.G., a Korea University grant (K2110581) to C.K. and with resources and the use of facilities at the Palo Alto Veterans Administration Healthcare System. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

    Publisher Copyright:
    © 2021, The Author(s).

    Keywords

    • Infectious disease
    • Memory T cells
    • Replication stress
    • T cell activation
    • T cell aging
    • T cell differentiation
    • Vaccine
    • miR-181a
    • microRNA

    ASJC Scopus subject areas

    • Immunology
    • Ageing

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