title: Dynamic expression of transcription factors T-bet and GATA-3 by regulatory T cells maintains immunotolerance.
abstract: Regulatory T cells (Treg cells) can express the transcription factors T-bet and GATA-3, but the function of this expression and whether such cells represent stable subsets is still unknown. By using various reporter tools, we found that the expression of T-bet and GATA-3 in Treg cells was dynamically influenced by the cytokine environment. Treg cell-specific deletion of the gene encoding either T-bet (Tbx21) or GATA-3 (Gata3) alone did not result in loss of Treg cell function; however, mice with combined deficiency in both genes in Treg cells developed severe autoimmune-like diseases. Loss of Treg cell function correlated with upregulation of expression of the transcription factor RORγt and reduced expression of the transcription factor Foxp3. Thus, in the steady state, activated Treg cells transiently upregulated either T-bet or GATA-3 to maintain T cell homeostasis.
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Yu
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Suveena
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Edwards
authors.affiliation: Laboratory Animal Sciences Program, National Cancer Institute, Frederick, Maryland, USA.
authors.forename: Lionel
authors.initials: L
authors.lastname: Feigenbaum
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Jinfang
authors.initials: J
authors.lastname: Zhu
mesh_terms: D000818:Animals; D015551:Autoimmunity; D002478:Cells, Cultured; D003092:Colitis / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D050990:GATA3 Transcription Factor / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation; D007108:Immune Tolerance / Q000235:genetics*; D051379:Mice; D020825:T-Box Domain Proteins / Q000235:genetics* / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D000098815:T-bet Transcription Factor
chemical_list: D050990:GATA3 Transcription Factor; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor