TY - JOUR
T1 - JNK2 modulates the CD1d-dependent and -independent activation of iNKT cells
AU - Liu, Jianyun
AU - Gallo, Richard M.
AU - Khan, Masood A.
AU - Iyer, Abhirami K.
AU - Kratzke, Ian M.
AU - Brutkiewicz, Randy R.
N1 - Funding Information:
Acknowledgements: We would like to thank the Flow Cytometry Resource Facility, Indiana University School of Medicine for their assistance. We also would like to thank the NIH Tetramer Core Facility for providing empty and PBS75-loaded CD1d tetramers. Drs. J. Yewdell, J. Bennink and D. Riese generously provided critical reagents. This work was supported by National Institutes of Health grants RO1 AI046455, RO1 CA161178 and P01 AI056097 (to R.R.B.), and U54 DK106846, supporting the Indiana University School of Medicine’s Cooperative Center of Excellence in Hematology.
Funding Information:
We would like to thank the Flow Cytometry Resource Facility, Indiana University School of Medicine for their assistance. We also would like to thank the NIH Tetramer Core Facility for providing empty and PBS75-loaded CD1d tetramers. Drs. J. Yewdell, J. Bennink and D. Riese generously provided critical reagents. This work was supported by National Institutes of Health grants RO1 AI046455, RO1 CA161178 and P01 AI056097 (to R.R.B.), and U54 DK106846, supporting the Indiana University School of Medicine's Cooperative Center of Excellence in Hematology.
Publisher Copyright:
© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2019/2
Y1 - 2019/2
N2 - 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.
AB - 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.
KW - Antigen processing and presentation
KW - CD1d
KW - NKT cells
KW - Signal transduction
KW - Viral infection
UR - http://www.scopus.com/inward/record.url?scp=85057740211&partnerID=8YFLogxK
U2 - 10.1002/eji.201847755
DO - 10.1002/eji.201847755
M3 - Article
C2 - 30467836
AN - SCOPUS:85057740211
SN - 0014-2980
VL - 49
SP - 255
EP - 265
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 2
ER -