Journal
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
Volume 73, Issue -, Pages 156-162Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.dci.2017.03.023
Keywords
Autoimmunity; FOXP3; Lymphoproliferation; Regulatory T cells; Zebrafish
Categories
Funding
- Japan Society for the Promotion of Science
- NHMRC [APP1032522, APP1046469]
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Regulatory T (T-reg) cells play a central role in the suppression of excessive immune responses against both self and non-self antigens. The development and function of T-reg cells are controlled by a master regulatory gene encoding the forkhead box P3 (FOXP3) protein in mammals. However, little is known regarding the functions of T-reg cells and FOXP3 in non-mammalian vertebrates. In this study, we generated mutant zebrafish lacking a functional FOXP3 ortholog, and demonstrated a significant reduction in survival accompanied by a marked increase in inflammatory gene expression, mononuclear cell infiltration, and T cell proliferation in peripheral tissues. Our findings indicate that the zebrafish FOXP3 protein may have an evolutionally conserved role in the control of immune tolerance, illuminating the potential of the zebrafish as a novel model for investigating the development and functions of T-reg cells. (C) 2017 Elsevier Ltd. All rights reserved.
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