Immuno-miRs: critical regulators of T-cell development, function and ageing

Authors

  • Bart-Jan Kroesen,

    1. Department of Laboratory Medicine, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
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  • Nato Teteloshvili,

    1. Department of Pathology and Medical Biology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
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  • Katarzyna Smigielska-Czepiel,

    1. Department of Pathology and Medical Biology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
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  • Elisabeth Brouwer,

    1. Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
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  • Anne Mieke H. Boots,

    1. Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
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  • Anke van den Berg,

    1. Department of Pathology and Medical Biology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
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  • Joost Kluiver

    Corresponding author
    1. Department of Pathology and Medical Biology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
    • Correspondence: J. Kluiver, University Medical Centre Groningen, Department of Pathology and Medical Biology (EA10), Hanzeplein 1, 9700 RB, Groningen, The Netherlands. Email: j.l.kluiver@umcg.nl

      Senior authors: Bart-Jan Kroesen and Joost Kluiver email: b.j.kroesen@umcg.nl

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Summary

MicroRNAs (miRNAs) are instrumental to many aspects of immunity, including various levels of T-cell immunity. Over the last decade, crucial immune functions were shown to be regulated by specific miRNAs. These ‘immuno-miRs’ regulate generic cell biological processes in T cells, such as proliferation and apoptosis, as well as a number of T-cell-specific features that are fundamental to the development, differentiation and function of T cells. In this review, we give an overview of the current literature with respect to the role of miRNAs at various stages of T-cell development, maturation, differentiation, activation and ageing. Little is known about the involvement of miRNAs in thymic T-cell development, although miR-181a and miR-150 have been implicated herein. In contrast, several broadly expressed miRNAs including miR-21, miR-155 and miR-17~92, have now been shown to regulate T-cell activation. Other miRNAs, including miR-146a, show a more T-cell-subset-specific expression pattern and are involved in the regulation of processes unique to that specific T-cell subset. Importantly, differences in the miRNA target gene repertoires of different T-cell subsets allow similar miRNAs to control different T-cell-subset-specific functions. Interestingly, several of the here described immuno-miRs have also been implicated in T-cell ageing and there are clear indications for causal involvement of miRNAs in immunosenescence. It is concluded that immuno-miRs have a dynamic regulatory role in many aspects of T-cell differentiation, activation, function and ageing. An important notion when studying miRNAs in relation to T-cell biology is that specific immuno-miRs may have quite unrelated functions in closely related T-cell subsets.

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