JNK2 modulates the CD1d-dependent and -independent activation of iNKT cells.
Eur J Immunol
; 49(2): 255-265, 2019 02.
Article
em En
| MEDLINE
| ID: mdl-30467836
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ativação Linfocitária
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Proteína Quinase 9 Ativada por Mitógeno
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Células T Matadoras Naturais
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Antígenos CD1d
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Eur J Immunol
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos