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Adaptive autoimmunity and Foxp3-based immunoregulation in zebrafish.

Francisco J Quintana1, Antonio H Iglesias, Mauricio F Farez

  • 1Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America. fquintana@rics.bwh.harvard.edu

Plos One
|March 12, 2010
PubMed
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Zebrafish exhibit adaptive autoimmunity and possess Foxp3-based immune regulation, challenging the notion that active self-tolerance is a recent evolutionary development. This discovery highlights zebrafish as a model for studying adaptive immunity and autoimmunity.

Area of Science:

  • Immunology
  • Evolutionary Biology
  • Zebrafish Research

Background:

  • Jawed vertebrates generate immune receptors via recombination, risking autoreactive lymphocytes.
  • Mammalian peripheral tolerance relies on Foxp3(+) regulatory T cells.
  • Teleosts use recombination, but active immunoregulation is considered a later evolutionary trait.

Purpose of the Study:

  • To characterize adaptive autoimmunity in zebrafish.
  • To investigate Foxp3-based immunoregulation in zebrafish.
  • To explore the evolutionary origins of self-tolerance mechanisms.

Main Methods:

  • Immunization of zebrafish with zebrafish central nervous system (zCNS) homogenate.
  • Cloning of the zebrafish Foxp3 ortholog (zFoxp3).

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  • Assessing zFoxp3's regulatory effects on mouse T cells and IL-17 production in zebrafish embryos.

    • Main Results:

    • Zebrafish immunization induced central nervous system (CNS) inflammation and specific antibodies.
    • Cloned zFoxp3 induced regulatory T cell phenotype in mouse T cells.
    • zFoxp3 demonstrated control over IL-17 production in zebrafish embryos.

    Conclusions:

    • Active self-tolerance mechanisms were acquired early in vertebrate evolution.
    • Regulatory mechanisms likely co-evolved with the potential for adaptive autoimmunity.
    • Zebrafish serve as a valuable model for dissecting adaptive immunity pathways.