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Related Experiment Videos

Flicr, a long noncoding RNA, modulates Foxp3 expression and autoimmunity.

David Zemmour1, Alvin Pratama1, Scott M Loughhead1

  • 1Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115.

Proceedings of the National Academy of Sciences of the United States of America
|April 12, 2017
PubMed
Summary
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A novel long noncoding RNA, Flicr, fine-tunes FoxP3 expression in regulatory T cells (Tregs). This regulation impacts Treg function, influencing autoimmune disease and antiviral immunity.

Area of Science:

  • Immunology
  • Molecular Biology
  • Epigenetics

Background:

  • Regulatory T cells (Tregs) are crucial for immune homeostasis, with FoxP3 expression being a key determinant of their function.
  • Gene expression in Tregs is tightly regulated by transcription factors, enhancers, and epigenetic modifications.
  • Long noncoding RNAs (lncRNAs) are emerging as important regulators of cellular processes, including immune cell function.

Purpose of the Study:

  • To investigate the role of the lncRNA Flicr in regulating FoxP3 expression in Tregs.
  • To elucidate the molecular mechanisms by which Flicr influences Treg activity.
  • To determine the physiological consequences of Flicr-mediated regulation in autoimmune and infectious disease models.

Main Methods:

  • Analysis of Flicr expression in mature Tregs.
Keywords:
Foxp3autoimmunitygene regulationlong noncoding RNAregulatory T cells

Related Experiment Videos

  • Investigation of Flicr's genomic location relative to FoxP3.
  • Assessment of Flicr's impact on chromatin accessibility at the FoxP3 locus.
  • Evaluation of Flicr's effects on Treg function in vitro and in vivo.
  • Studies in conditions of IL-2 deficiency and IL-2 treatment.
  • Main Results:

    • Flicr acts as a negative regulator of FoxP3 expression, leading to reduced FoxP3 protein levels in a subset of Tregs.
    • Flicr functions in cis, specifically modulating chromatin accessibility at the CNS3/AR5 region of the FoxP3 locus without affecting DNA methylation.
    • Flicr expression is inversely regulated by IL-2, with IL-2 deficiency enhancing Flicr levels.
    • Curtailment of Treg activity by Flicr promotes autoimmune diabetes and restrains antiviral responses.

    Conclusions:

    • Flicr represents a novel layer of epigenetic control over FoxP3 expression in Tregs.
    • This Flicr-FoxP3 regulatory axis plays a significant role in balancing immune tolerance and immune responses.
    • The Flicr mechanism may allow for Treg-mediated immune evasion during infection or cancer, albeit with an increased risk of autoimmunity.