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In humans, FOXP1 expression has been correlated with overall survival in patients with peripheral T\u2010cell lymphoma (PTCL), although its regulatory role in T\u2010cell function is currently unknown. We found that FOXP1 is normally expressed in all human leukocyte subpopulations. Focusing on primary human CD4<jats:sup>+<\/jats:sup> T cells, we show that nuclear expression of FOXP1 predominates in na\u00efve cells with significant downregulation detected in memory cells from blood and tonsils. FOXP1 is repressed following in vitro T\u2010cell activation of na\u00efve T cells, and later re\u2010established in memory CD4<jats:sup>+<\/jats:sup> T cells, albeit at lower levels. DNA methylation analysis revealed that epigenetic mechanisms participate in regulating the human <jats:italic>FOXP1<\/jats:italic> gene. ShRNA\u2010mediated FOXP1 repression induces CD4<jats:sup>+<\/jats:sup> T cells to enter the cell cycle, acquire memory\u2010like markers and upregulate helper T\u2010cell differentiation genes. In patients with lymphoproliferative disorders, FOXP1 expression is constitutionally repressed in the clonal T cells in parallel with overexpression of helper T\u2010cell differentiation genes. Collectively, these data identify FOXP1 as an essential transcriptional regulator for primary human CD4<jats:sup>+<\/jats:sup> T cells and suggest its potential important role in the development of PTCL.<\/jats:p>","DOI":"10.1002\/eji.201646373","type":"journal-article","created":{"date-parts":[[2016,11,8]],"date-time":"2016-11-08T08:24:40Z","timestamp":1478593480000},"page":"168-179","source":"Crossref","is-referenced-by-count":36,"title":["FOXP1 is a regulator of quiescence in healthy human CD4<sup>+<\/sup> T cells and is constitutively repressed in T cells from patients with lymphoproliferative disorders"],"prefix":"10.1002","volume":"47","author":[{"given":"Soizic","family":"Garaud","sequence":"first","affiliation":[{"name":"Molecular Immunology Unit Institut Jules Bordet Universit\u00e9 Libre de Bruxelles  Brussels Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florence","family":"Roufosse","sequence":"additional","affiliation":[{"name":"Department of 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