title: The transcription factor STAT3 is required for T helper 2 cell development.
abstract: Signal transducer and activator of transcription (STAT) family members direct the differentiation of T helper cells, with specific STAT proteins promoting distinct effector subsets. STAT6 is required for the development of T helper 2 (Th2) cells, whereas STAT3 promotes differentiation of Th17 and follicular helper T cell subsets. We demonstrated that STAT3 was also activated during Th2 cell development and was required for the expression of Th2 cell-associated cytokines and transcription factors. STAT3 bound directly to Th2 cell-associated gene loci and was required for the ability of STAT6 to bind target genes. In vivo, STAT3 deficiency in T cells eliminated the allergic inflammation in mice sensitized and challenged with ovalbumin or transgenic for constitutively active STAT6. Thus, STAT3 cooperates with STAT6 in promoting Th2 cell development. These results demonstrate that differentiating T helper cells integrate multiple STAT protein signals during Th2 cell development.
authors.affiliation: Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Gretta L
authors.initials: GL
authors.lastname: Stritesky
authors.forename: Rajarajeswari
authors.initials: R
authors.lastname: Muthukrishnan
authors.forename: Sarita
authors.initials: S
authors.lastname: Sehra
authors.forename: Ritobrata
authors.initials: R
authors.lastname: Goswami
authors.forename: Duy
authors.initials: D
authors.lastname: Pham
authors.forename: Jared
authors.initials: J
authors.lastname: Travers
authors.forename: Evelyn T
authors.initials: ET
authors.lastname: Nguyen
authors.forename: David E
authors.initials: DE
authors.lastname: Levy
authors.forename: Mark H
authors.initials: MH
authors.lastname: Kaplan
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011485:Protein Binding / Q000276:immunology; D020239:Receptor Cross-Talk / Q000276:immunology; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015533:Transcriptional Activation
chemical_list: D016207:Cytokines; D050796:STAT3 Transcription Factor; D050800:STAT6 Transcription Factor