Regulation of immune responses and tolerance: the microRNA perspective

Authors

  • Chang-Zheng Chen,

    Corresponding author
    1. Department of Microbiology and Immunology, Baxter Laboratory in Stem Cell Biology, Stanford University School of Medicine, Stanford, CA, USA
    • Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA
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  • Steven Schaffert,

    1. Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA
    2. Department of Microbiology and Immunology, Baxter Laboratory in Stem Cell Biology, Stanford University School of Medicine, Stanford, CA, USA
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  • Rita Fragoso,

    1. Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA
    2. Department of Microbiology and Immunology, Baxter Laboratory in Stem Cell Biology, Stanford University School of Medicine, Stanford, CA, USA
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  • Christina Loh

    1. Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA
    2. Department of Microbiology and Immunology, Baxter Laboratory in Stem Cell Biology, Stanford University School of Medicine, Stanford, CA, USA
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Correspondence to:

Chang-Zheng Chen

Department of Microbiology and Immunology

Baxter Laboratory in Stem Cell Biology, Stanford University School of Medicine

269 Campus Drive CCSR 3205B

Stanford, CA 94305, USA

Tel.: +1 650 725 1667

Fax: +1 650 723 2383

e-mail: czchen@stanford.edu

Summary

Much has been learned about the molecular and cellular components critical for the control of immune responses and tolerance. It remains a challenge, however, to control the immune response and tolerance at the system level without causing significant toxicity to normal tissues. Recent studies suggest that microRNA (miRNA) genes, an abundant class of non-coding RNA genes that produce characteristic approximately 22 nucleotides small RNAs, play important roles in immune cells. In this article, we discuss emerging knowledge regarding the functions of miRNA genes in the immune system. We delve into the roles of miRNAs in regulating signaling strength and threshold, homeostasis, and the dynamics of the immune response and tolerance during normal and pathogenic immunological conditions. We also present observations based on analyzes of miR-181 family genes that indicate the potential functions of primary and/or precursor miRNAs in target recognition and explore the impact of these findings on target identification. Finally, we illustrate that despite the subtle effects of miRNAs on gene expression, miRNAs have the potential to influence the outcomes of normal and pathogenic immune responses by controlling the quantitative and dynamic aspects of immune responses. Tuning miRNA functions in immune cells, through gain- and loss-of-function approaches in mice, may reveal novel approach to restore immune equilibrium from pathogenic conditions, such as autoimmune disease and leukemia, without significant toxicity.

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