title: STAT3 promotes CD1d-mediated lipid antigen presentation by regulating a critical gene in glycosphingolipid biosynthesis.
abstract: Cytokines that regulate the immune response signal through the Janus kinase / signal transducer and activation of transcription (JAK/STAT) pathway, but whether this pathway can regulate CD1d-mediated lipid antigen presentation to natural killer T (NKT) cells is unknown. Here, we found that STAT3 promotes antigen presentation by CD1d. Antigen-presenting cells (APCs) in which STAT3 expression was inhibited exhibited markedly reduced endogenous lipid antigen presentation to NKT cells without an impact on exogenous lipid antigen presentation by CD1d. Consistent with this observation, in APCs where STAT3 was knocked down, dramatically decreased levels of UDP glucose ceramide glucosyltransferase (UGCG), an enzyme involved in the first step of glycosphingolipid biosynthesis, were observed. Impaired lipid antigen presentation was reversed by ectopic expression of UGCG in STAT3-silenced CD1d(+) APCs. Hence, by controlling a fundamental step in CD1d-mediated lipid antigen presentation, STAT3 signalling promotes innate immune responses driven by CD1d.
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Abhirami K
authors.initials: AK
authors.lastname: Iyer
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Jianyun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Gallo
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA.|Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Kaplan
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Randy R
authors.initials: RR
authors.lastname: Brutkiewicz
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D055610:Antigens, CD1d / Q000378:metabolism*; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D005964:Glucosyltransferases / Q000378:metabolism; D006028:Glycosphingolipids / Q000096:biosynthesis*; D057809:HEK293 Cells; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D008055:Lipids / Q000276:immunology*; D051379:Mice; D055611:Natural Killer T-Cells / Q000276:immunology / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology
chemical_list: D055610:Antigens, CD1d; C526877:CD1D protein, human; C584692:CD1d antigen, mouse; D006028:Glycosphingolipids; D000949:Histocompatibility Antigens Class II; D008055:Lipids; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D005964:Glucosyltransferases; C023246:ceramide glucosyltransferase
keywords: Janus kinase / signal transducer and activation of transcription; antigen presentation; signal transduction