title: Zebrafish FOXP3 is required for the maintenance of immune tolerance.
abstract: Regulatory T (Treg) cells play a central role in the suppression of excessive immune responses against both self and non-self antigens. The development and function of Tregcells are controlled by a master regulatory gene encoding the forkhead box P3 (FOXP3) protein in mammals. However, little is known regarding the functions of Tregcells 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 Tregcells.
authors.affiliation: Developmental and Stem Cell Biology Division, Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Sugimoto
authors.affiliation: Developmental and Stem Cell Biology Division, Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia.
authors.forename: Subhra P
authors.initials: SP
authors.lastname: Hui
authors.affiliation: Developmental and Stem Cell Biology Division, Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia.
authors.forename: Delicia Z
authors.initials: DZ
authors.lastname: Sheng
authors.affiliation: Developmental and Stem Cell Biology Division, Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia.
authors.forename: Maki
authors.initials: M
authors.lastname: Nakayama
authors.affiliation: Developmental and Stem Cell Biology Division, Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia; St. Vincent's Clinical School, University of New South Wales, Kensington, NSW 2052, Australia. Electronic address: k.kikuchi@victorchang.edu.au.
authors.forename: Kazu
authors.initials: K
authors.lastname: Kikuchi
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D051858:Forkhead Transcription Factors / Q000276:immunology*; D017634:Self Tolerance / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D015027:Zebrafish / Q000276:immunology*; D029961:Zebrafish Proteins / Q000276:immunology*
chemical_list: D051858:Forkhead Transcription Factors; D029961:Zebrafish Proteins; C554833:foxp3a protein, zebrafish
keywords: Autoimmunity; FOXP3; Lymphoproliferation; Regulatory T cells; Zebrafish