title: FOXP1 is a regulator of quiescence in healthy human CD4+T cells and is constitutively repressed in T cells from patients with lymphoproliferative disorders.
abstract: The forkhead box P1 (FOXP1) transcription factor has been shown to regulate the generation and maintenance of quiescent naïve murine T cells. In humans, FOXP1 expression has been correlated with overall survival in patients with peripheral T-cell lymphoma (PTCL), although its regulatory role in T-cell function is currently unknown. We found that FOXP1 is normally expressed in all human leukocyte subpopulations. Focusing on primary human CD4+T cells, we show that nuclear expression of FOXP1 predominates in naïve cells with significant downregulation detected in memory cells from blood and tonsils. FOXP1 is repressed following in vitro T-cell activation of naïve T cells, and later re-established in memory CD4+T cells, albeit at lower levels. DNA methylation analysis revealed that epigenetic mechanisms participate in regulating the human FOXP1 gene. ShRNA-mediated FOXP1 repression induces CD4+T cells to enter the cell cycle, acquire memory-like markers and upregulate helper T-cell differentiation genes. In patients with lymphoproliferative disorders, FOXP1 expression is constitutionally repressed in the clonal T cells in parallel with overexpression of helper T-cell differentiation genes. Collectively, these data identify FOXP1 as an essential transcriptional regulator for primary human CD4+T cells and suggest its potential important role in the development of PTCL.
authors.affiliation: Molecular Immunology Unit, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Soizic
authors.initials: S
authors.lastname: Garaud
authors.affiliation: Department of Internal Medicine, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.|Institute for Medical Immunology, Université Libre de Bruxelles, Gosselies, Belgium.
authors.forename: Florence
authors.initials: F
authors.lastname: Roufosse
authors.affiliation: Molecular Immunology Unit, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Pushpamali
authors.initials: P
authors.lastname: De Silva
authors.affiliation: Molecular Immunology Unit, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Gu-Trantien
authors.affiliation: Molecular Immunology Unit, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Jean-Nicolas
authors.initials: JN
authors.lastname: Lodewyckx
authors.affiliation: Molecular Immunology Unit, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.|Flow Cytometry Core Facility, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Hugues
authors.initials: H
authors.lastname: Duvillier
authors.affiliation: Laboratory of Cancer Epigenetics, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Sarah
authors.initials: S
authors.lastname: Dedeurwaerder
authors.affiliation: Laboratory of Cancer Epigenetics, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Martin
authors.initials: M
authors.lastname: Bizet
authors.affiliation: Laboratory of Cancer Epigenetics, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Defrance
authors.affiliation: Laboratory of Cancer Epigenetics, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: François
authors.initials: F
authors.lastname: Fuks
authors.affiliation: Institut de Recherches Microbiologiques J-M Wiame, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Françoise
authors.initials: F
authors.lastname: Bex
authors.affiliation: Molecular Immunology Unit, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Karen
authors.initials: K
authors.lastname: Willard-Gallo
mesh_terms: D015415:Biomarkers; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002453:Cell Cycle / Q000235:genetics; D002460:Cell Line; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D016130:Immunophenotyping; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D010641:Phenotype; D011401:Promoter Regions, Genetic; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C486626:FOXP1 protein, human; D051858:Forkhead Transcription Factors; D011948:Receptors, Antigen, T-Cell; D012097:Repressor Proteins
keywords: CD4+ T cells; FOXP1; lymphocytic variant hypereosinophilic syndrome; quiescence