6533b862fe1ef96bd12c623e
RESEARCH PRODUCT
The transcription factor IRF1 dictates the IL-21-dependent anticancer functions of TH9 cells
Lionel ApetohGrégoire MignotValentin DerangèreFanny ChalminHélène BergerRomain BoidotMélanie BruchardMagalie DossetCédric RébéFrançois GhiringhelliBernhard RyffelFrédérique VégranMasashi KatoArmelle Prévost-blondelsubject
OvalbuminGreen Fluorescent ProteinsImmunologyMelanoma ExperimentalProto-Oncogene Proteins c-fyn3T3 cellsCell LineInterferon-gammaMicemedicineAnimalsImmunology and AllergySTAT1PhosphorylationRNA Small InterferingSTAT4Transcription factorInterleukin 3Mice KnockoutBase SequencebiologySequence Analysis RNAChemistryEffectorInterleukinsInterleukin-9Promoter3T3 CellsT-Lymphocytes Helper-InducerInterleukin-10Cell biologyMice Inbred C57BLSTAT1 Transcription Factormedicine.anatomical_structureCell culturebiology.proteinFemaleRNA InterferenceInterferon Regulatory Factor-1description
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2014-06-29 | Nature Immunology |