title: A novel isoform of the orphan receptor RORγt suppresses IL-17 production in human T cells.
abstract: T helper (Th)17 cells constitute a distinct subset of CD4(+) helper T cells that is mainly characterized by abundant interleukin (IL)-17 production and is involved in the host defence against bacteria and fungi as well as in the pathogenesis of autoimmune diseases. The retinoic orphan receptor (ROR)γt directs the transcriptional activation of the IL17 gene. Here, we report the presence of a novel RORγt isoform, RORγt-Δ(5-8), which lacks the hinge-encoding exons 5-8 and represses potently IL17 and IL21 gene transcription. It thereby reduces the expression of multiple Th17-assigned cytokines. We propose that RORγt-Δ(5-8) acts as a dominant-negative regulator of RORγt-mediated gene regulation and the balance between the full-length RORγt and the novel repressor isoform may arbitrate IL-17 production in human T cells.
authors.affiliation: Department of Medicine, Division of Rheumatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: T
authors.initials: T
authors.lastname: Rauen
authors.forename: Y-T
authors.initials: YT
authors.lastname: Juang
authors.forename: C M
authors.initials: CM
authors.lastname: Hedrich
authors.forename: K
authors.initials: K
authors.lastname: Kis-Toth
authors.forename: G C
authors.initials: GC
authors.lastname: Tsokos
mesh_terms: D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology*; D007378:Interleukins / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000276:immunology*; D010957:Plasmids / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D014158:Transcription, Genetic; D014162:Transfection / Q000379:methods; D000098546:Interleukin-21
chemical_list: C508717:IL17A protein, human; D020381:Interleukin-17; D007378:Interleukins; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D020033:Protein Isoforms; C539900:RORC protein, human; D012097:Repressor Proteins; D007371:Interferon-gamma; D000098546:Interleukin-21