STAT3 promotes CD1d-mediated lipid antigen presentation by regulating a critical gene in glycosphingolipid biosynthesis

Abhirami K. Iyer, Jianyun Liu, Richard M. Gallo, Mark Kaplan, Randy Brutkiewicz

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)444-455
Number of pages12
JournalImmunology
Volume146
Issue number3
DOIs
StatePublished - Nov 1 2015

Fingerprint

Glycosphingolipids
Antigen Presentation
ceramide glucosyltransferase
Lipids
Antigen-Presenting Cells
Genes
Natural Killer T-Cells
CD1d Antigen
Janus Kinases
Transducers
Innate Immunity
Transcriptional Activation
Cytokines
Enzymes

Keywords

  • Antigen presentation
  • Janus kinase / signal transducer and activation of transcription
  • Signal transduction

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

STAT3 promotes CD1d-mediated lipid antigen presentation by regulating a critical gene in glycosphingolipid biosynthesis. / Iyer, Abhirami K.; Liu, Jianyun; Gallo, Richard M.; Kaplan, Mark; Brutkiewicz, Randy.

In: Immunology, Vol. 146, No. 3, 01.11.2015, p. 444-455.

Research output: Contribution to journalArticle

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AU - Brutkiewicz, Randy

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