title: The transcription factor IRF1 dictates the IL-21-dependent anticancer functions of TH9 cells.
abstract: The TH9 subset of helper T cells was initially shown to contribute to the induction of autoimmune and allergic diseases, but subsequent evidence has suggested that these cells also exert antitumor activities. However, the molecular events that account for their effector properties are elusive. Here we found that the transcription factor IRF1 enhanced the effector function of TH9 cells and dictated their anticancer properties. Under TH9-skewing conditions, interleukin 1β (IL-1β) induced phosphorylation of the transcription factor STAT1 and subsequent expression of IRF1, which bound to the promoters of Il9 and Il21 and enhanced secretion of the cytokines IL-9 and IL-21 from TH9 cells. Furthermore, IL-1β-induced TH9 cells exerted potent anticancer functions in an IRF1- and IL-21-dependent manner. Our findings thus identify IRF1 as a target for controlling the function of TH9 cells.
authors: 1] INSERM, U866, Dijon, France. [2] Faculté de Médecine, Université de Bourgogne, Dijon, France. [3].
authors: Frédérique
authors: F
authors: Végran
authors: 1] INSERM, U866, Dijon, France. [2] Faculté de Médecine, Université de Bourgogne, Dijon, France. [3].
authors: Hélène
authors: H
authors: Berger
authors: Centre Georges François Leclerc, Dijon, France.
authors: Romain
authors: R
authors: Boidot
authors: 1] INSERM, U866, Dijon, France. [2] Faculté de Médecine, Université de Bourgogne, Dijon, France.
authors: Grégoire
authors: G
authors: Mignot
authors: 1] INSERM, U866, Dijon, France. [2] Faculté de Médecine, Université de Bourgogne, Dijon, France.
authors: Mélanie
authors: M
authors: Bruchard
authors: 1] INSERM, U866, Dijon, France. [2] Faculté de Médecine, Université de Bourgogne, Dijon, France.
authors: Magalie
authors: M
authors: Dosset
authors: 1] INSERM, U866, Dijon, France. [2] Faculté de Médecine, Université de Bourgogne, Dijon, France.
authors: Fanny
authors: F
authors: Chalmin
authors: 1] INSERM, U866, Dijon, France. [2] Faculté de Médecine, Université de Bourgogne, Dijon, France. [3] Centre Georges François Leclerc, Dijon, France.
authors: Cédric
authors: C
authors: Rébé
authors: 1] INSERM, U866, Dijon, France. [2] Faculté de Médecine, Université de Bourgogne, Dijon, France.
authors: Valentin
authors: V
authors: Dérangère
authors: 1] CNRS and University, UMR7355, Orléans, France. [2] Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa.
authors: Bernhard
authors: B
authors: Ryffel
authors: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Aichi, Japan.
authors: Masashi
authors: M
authors: Kato
authors: 1] CNRS, UMR 8104, Paris, France. [2] INSERM, U1016, Paris, France. [3] Paris Descartes University, Cochin Institute, Paris, France.
authors: Armelle
authors: A
authors: Prévost-Blondel
authors: 1] INSERM, U866, Dijon, France. [2] Faculté de Médecine, Université de Bourgogne, Dijon, France. [3] Centre Georges François Leclerc, Dijon, France. [4].
authors: François
authors: F
authors: Ghiringhelli
authors: 1] INSERM, U866, Dijon, France. [2] Faculté de Médecine, Université de Bourgogne, Dijon, France. [3] Centre Georges François Leclerc, Dijon, France. [4].
authors: Lionel
authors: L
authors: Apetoh
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D005260:Female; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D050856:Interferon Regulatory Factor-1 / Q000096:biosynthesis / Q000276:immunology*; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000276:immunology; D016906:Interleukin-9 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008546:Melanoma, Experimental / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D010766:Phosphorylation / Q000276:immunology; D051076:Proto-Oncogene Proteins c-fyn / Q000037:antagonists & inhibitors / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering; D050794:STAT1 Transcription Factor / Q000276:immunology; D017423:Sequence Analysis, RNA; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D000098546:Interleukin-21
chemical_list: C556062:IL10 protein, mouse; D050856:Interferon Regulatory Factor-1; D016906:Interleukin-9; D007378:Interleukins; C494258:Irf1 protein, mouse; D034741:RNA, Small Interfering; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D016753:Interleukin-10; D049452:Green Fluorescent Proteins; D007371:Interferon-gamma; D010047:Ovalbumin; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn; D000098546:Interleukin-21