title: Cutting edge: The transcription factor Kruppel-like factor 4 regulates the differentiation of Th17 cells independently of RORγt.
abstract: Th17 cells play a significant role in inflammatory and autoimmune responses. Although a number of molecular pathways that contribute to the lineage differentiation of T cells have been discovered, the mechanisms by which lineage commitment occurs are not fully understood. Transcription factors play a key role in driving T cells toward specific lineages. We have identified a role for the transcription factor Kruppel-like factor (KLF) 4 in the development of IL-17-producing CD4(+) T cells. KLF4 was required for the production of IL-17, and further, chromatin immunoprecipitation analysis demonstrated binding of KLF4 to the IL-17 promoter, indicating a direct effect on the regulation of IL-17. Further, KLF4-deficient T cells upregulated expression of retinoic acid-related orphan receptor γt similar to wild-type during the polarization process toward Th17, suggesting that these two transcription factors are regulated independently.
authors.affiliation: Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Lori
authors.initials: L
authors.lastname: Lebson
authors.forename: Anne
authors.initials: A
authors.lastname: Gocke
authors.forename: Jason
authors.initials: J
authors.lastname: Rosenzweig
authors.forename: Jonathan
authors.initials: J
authors.lastname: Alder
authors.forename: Curt
authors.initials: C
authors.lastname: Civin
authors.forename: Peter A
authors.initials: PA
authors.lastname: Calabresi
authors.forename: Katharine A
authors.initials: KA
authors.lastname: Whartenby
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000276:immunology*; D011401:Promoter Regions, Genetic / Q000235:genetics / Q000276:immunology*; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology*; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology*
chemical_list: D020381:Interleukin-17; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3