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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
Summary
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).
- 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.
