title: Type I interferon-enhanced IL-10 expression in human CD4 T cells is regulated by STAT3, STAT2, and BATF transcription factors.
abstract: Type I IFN can exert pro- and anti-inflammatory activities in the immune system. Here, we have investigated the mechanism by which IFN-α enhances early expression of the anti-inflammatory cytokine IL-10 in human CD45RA+CD4+T cells. With the use of transcriptomic and biochemical approaches, we found distinct and combined contributions of the IFN and the TCR signaling pathways to the induction ofSTAT1/2/3and the basic leucine zipper activating transcription factor-like (BATF) family members. Moreover, IFN-induced STAT3 phosphorylation was prolonged by the TCR response, whereas IFN-induced STAT2 phosphorylation was of long duration. With the use of RNA interference (RNAi), we identified STAT3 as the major actor and STAT2 as a contributor of the IFN action onIL-10Upon TCR/IFN costimulation, STAT3 directly bound at theIL-10conserved noncoding sequence (CNS)- 9, an enhancer element known to recruit BATF in CD4 T cells. The cosilencing of the 3BATFsresulted in an overall reduction ofIL-10expression, but the promoting activity of IFN-α was retained. These results support the notion that the IFN action is indexed on BATF function and provide evidence for a cooperation between BATFs and STAT3, the latter being activated via early IFN and delayed TCR effects.
authors.affiliation: Institut Pasteur, Unit of Cytokine Signaling, Paris, France; and.|Centre National de la Recherche Scientifique URA1961, Institut National de la Santé et de la Recherche Médicale U1221, Paris, France.
authors.forename: Umeshree
authors.initials: U
authors.lastname: Govender
authors.affiliation: Institut Pasteur, Unit of Cytokine Signaling, Paris, France; and.|Centre National de la Recherche Scientifique URA1961, Institut National de la Santé et de la Recherche Médicale U1221, Paris, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Corre
authors.affiliation: Institut Pasteur, Unit of Cytokine Signaling, Paris, France; and.|Centre National de la Recherche Scientifique URA1961, Institut National de la Santé et de la Recherche Médicale U1221, Paris, France.
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Bourdache
authors.affiliation: Institut Pasteur, Unit of Cytokine Signaling, Paris, France; and.|Centre National de la Recherche Scientifique URA1961, Institut National de la Santé et de la Recherche Médicale U1221, Paris, France.
authors.forename: Sandra
authors.initials: S
authors.lastname: Pellegrini
authors.affiliation: Institut Pasteur, Unit of Cytokine Signaling, Paris, France; and frederique.michel@pasteur.fr.|Centre National de la Recherche Scientifique URA1961, Institut National de la Santé et de la Recherche Médicale U1221, Paris, France.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Michel
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D050976:Basic-Leucine Zipper Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D001665:Binding Sites; D018106:CD28 Antigens / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D017252:CD3 Complex / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D003513:Cycloheximide / Q000494:pharmacology; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology / Q000494:pharmacology*; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology*; D010766:Phosphorylation / Q000187:drug effects; D061251:Primary Cell Culture; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D050795:STAT2 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction
chemical_list: D000906:Antibodies; C099359:BATF protein, human; D050976:Basic-Leucine Zipper Transcription Factors; D018106:CD28 Antigens; D017252:CD3 Complex; C508609:IL10 protein, human; D016898:Interferon-alpha; D020033:Protein Isoforms; D034741:RNA, Small Interfering; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050795:STAT2 Transcription Factor; C494084:STAT2 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D016753:Interleukin-10; D003513:Cycloheximide
keywords: Tr1 cells; gene regulation; signaling