JNK2 modulates the CD1d-dependent and -independent activation of iNKT cells

Jianyun Liu, Richard M. Gallo, Masood A. Khan, Abhirami K. Iyer, Ian M. Kratzke, Randy Brutkiewicz

Research output: Contribution to journalArticle

Abstract

Invariant natural killer T (iNKT) cells play critical roles in autoimmune, anti-tumor, and anti-microbial immune responses, and are activated by glycolipids presented by the MHC class I-like molecule, CD1d. How the activation of signaling pathways impacts antigen (Ag)-dependent iNKT cell activation is not well-known. In the current study, we found that the MAPK JNK2 not only negatively regulates CD1d-mediated Ag presentation in APCs, but also contributes to CD1d-independent iNKT cell activation. A deficiency in the JNK2 (but not JNK1) isoform enhanced Ag presentation by CD1d. Using a vaccinia virus (VV) infection model known to cause a loss in iNKT cells in a CD1d-independent, but IL-12-dependent manner, we found the virus-induced loss of iNKT cells in JNK2 KO mice was substantially lower than that observed in JNK1 KO or wild-type (WT) mice. Importantly, compared to WT mice, JNK2 KO mouse iNKT cells were found to express less surface IL-12 receptors. As with a VV infection, an IL-12 injection also resulted in a smaller decrease in JNK2 KO iNKT cells as compared to WT mice. Overall, our work strongly suggests JNK2 is a negative regulator of CD1d-mediated Ag presentation and contributes to IL-12-induced iNKT cell activation and loss during viral infections.

Original languageEnglish (US)
JournalEuropean Journal of Immunology
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

CD1d Antigen
Antigen Presentation
Virus Diseases
Interleukin-12
Vaccinia virus
Interleukin-12 Receptors
Natural Killer T-Cells
Glycolipids
Protein Isoforms
Viruses
Antigens
Injections
Neoplasms

Keywords

  • Antigen processing and presentation
  • CD1d
  • NKT cells
  • Signal transduction
  • Viral infection

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

JNK2 modulates the CD1d-dependent and -independent activation of iNKT cells. / Liu, Jianyun; Gallo, Richard M.; Khan, Masood A.; Iyer, Abhirami K.; Kratzke, Ian M.; Brutkiewicz, Randy.

In: European Journal of Immunology, 01.01.2018.

Research output: Contribution to journalArticle

Liu, Jianyun ; Gallo, Richard M. ; Khan, Masood A. ; Iyer, Abhirami K. ; Kratzke, Ian M. ; Brutkiewicz, Randy. / JNK2 modulates the CD1d-dependent and -independent activation of iNKT cells. In: European Journal of Immunology. 2018.
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