title: Transcription factor Foxp1 exerts essential cell-intrinsic regulation of the quiescence of naive T cells.
abstract: The molecular mechanisms that underlie T cell quiescence are poorly understood. Here we report that mature naive CD8(+) T cells lacking the transcription factor Foxp1 gained effector phenotype and function and proliferated directly in response to interleukin 7 (IL-7) in vitro. Foxp1 repressed expression of the IL-7 receptor α-chain (IL-7Rα) by antagonizing Foxo1 and negatively regulated signaling by the kinases MEK and Erk. Acute deletion of Foxp1 induced naive T cells to gain an effector phenotype and proliferate in lympho-replete mice. Foxp1-deficient naive CD8(+) T cells proliferated even in lymphopenic mice deficient in major histocompatibility complex class I. Our results demonstrate that Foxp1 exerts essential cell-intrinsic regulation of naive T cell quiescence, providing direct evidence that lymphocyte quiescence is achieved through actively maintained mechanisms that include transcriptional regulation.
authors.affiliation: The Wistar Institute, Philadelphia, Pennsylvania, USA.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Feng
authors.forename: Haikun
authors.initials: H
authors.lastname: Wang
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takata
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Day
authors.forename: Jessica
authors.initials: J
authors.lastname: Willen
authors.forename: Hui
authors.initials: H
authors.lastname: Hu
mesh_terms: D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D015151:Immunoblotting; D015851:Interleukin-7 / Q000494:pharmacology; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009570:Nitriles / Q000494:pharmacology; D011485:Protein Binding; D011725:Pyridines / Q000494:pharmacology; D020395:Receptors, Interleukin-7 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
chemical_list: D002070:Butadienes; D004791:Enzyme Inhibitors; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; C432917:Foxp1 protein, mouse; D007093:Imidazoles; D015851:Interleukin-7; D009570:Nitriles; D011725:Pyridines; D020395:Receptors, Interleukin-7; D012097:Repressor Proteins; C113580:U 0126; C415350:interleukin-7 receptor, alpha chain; D048049:Extracellular Signal-Regulated MAP Kinases; D020930:MAP Kinase Kinase Kinases; C093642:SB 203580