title: Regulatory T cells suppress CD4+ T cells through NFAT-dependent transcriptional mechanisms.
abstract: Regulatory T cells (Tregs) control autoreactive T cells by inhibiting activation-induced proliferation and cytokine expression. The molecular mechanisms responsible for the inactivation of effector T cells by Tregs remain yet to be fully characterized. We report that T-helper cells stimulated in the presence of Tregs quickly activate NFAT1 and have increased NFAT1-dependent expression of the transcription repressor Ikaros. NFAT1 deficiency or dominant-negative Ikaros compromises Treg-mediated inhibition of T-helper cells in vitro and in vivo. Thus, our results place NFAT-dependent mechanisms as general regulators of T-cell tolerance and show that Treg-mediated suppression of T-helper cells results from the activation of NFAT-regulated gene expression.
authors: Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA.
authors: Daniel S
authors: DS
authors: Shin
authors: Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA.
authors: Ayana
authors: A
authors: Jordan
authors: Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA.
authors: Samik
authors: S
authors: Basu
authors: Department of Pathology and Laboratory Medicine, Perelman School of Medicine University of Pennsylvania and Children's Hospital of Philadelphia Research Institute, Philadelphia, PA, USA.
authors: Rajan M
authors: RM
authors: Thomas
authors: Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA.
authors: Sanmay
authors: S
authors: Bandyopadhyay
authors: Department of Pathology and Laboratory Medicine, Perelman School of Medicine University of Pennsylvania and Children's Hospital of Philadelphia Research Institute, Philadelphia, PA, USA.
authors: Edwin F
authors: EF
authors: de Zoeten
authors: Department of Pathology and Laboratory Medicine, Perelman School of Medicine University of Pennsylvania and Children's Hospital of Philadelphia Research Institute, Philadelphia, PA, USA.
authors: Andrew D
authors: AD
authors: Wells
authors: Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA fernando.macian@einstein.yu.edu.
authors: Fernando
authors: F
authors: Macian
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis; D005786:Gene Expression Regulation; D051740:Ikaros Transcription Factor / Q000096:biosynthesis* / Q000235:genetics; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D050778:NFATC Transcription Factors / Q000096:biosynthesis / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
chemical_list: D016207:Cytokines; D050778:NFATC Transcription Factors; C494007:Nfatc2 protein, mouse; C497238:Zfpn1a1 protein, mouse; D051740:Ikaros Transcription Factor
keywords: Ikaros; NFAT; regulatory T cell