Author:
Trittel Stephanie,Chambers Benedict J.,Heise Ulrike,Guzmán Carlos A.,Riese Peggy
Abstract
AbstractThe contribution of natural killer (NK) cells to the clearance of hepatic viral infections is well recognized. The recently discovered heterogeneity of NK cell populations renders them interesting targets for immune interventions. Invariant natural killer T (iNKT) cells represent a key interaction partner for hepatic NK cells. The present study addressed whether characteristics of NK cells in the liver can be shaped by targeting iNKT cells. For this, the CD1d-binding pegylated glycolipid αGalCerMPEG was assessed for its ability to modulate the features of NK cells permanently or transiently residing in the liver.In vivoadministration resulted in enhanced functionality of educated and highly differentiated CD27+Mac-1+NK cells accompanied by an increased proliferation. Improved liver homing was supported by serum-derived and cellular factors. Reduced viral loads in a mCMV infection model confirmed the beneficial effect of NK cells located in the liver upon stimulation with αGalCerMPEG. Thus, targeting iNKT cell-mediated NK cell activation in the liver represents a promising approach for the establishment of liver-directed immune interventions.
Publisher
Springer Science and Business Media LLC
Reference115 articles.
1. Vivier, E., Tomasello, E., Baratin, M., Walzer, T. & Ugolini, S. Functions of natural killer cells. Nat Immunol 9, 503–510, https://doi.org/10.1038/ni1582 (2008).
2. Perussia, B. Lymphokine-activated killer cells, natural killer cells and cytokines. Curr Opin Immunol 3, 49–55 (1991).
3. Shi, F. D., Ljunggren, H. G. & Sarvetnick, N. Innate immunity and autoimmunity: from self-protection to self-destruction. Trends Immunol 22, 97–101 (2001).
4. Wilder, J. A., Koh, C. Y. & Yuan, D. The role of NK cells during in vivo antigen-specific antibody responses. J Immunol 156, 146–152 (1996).
5. Hoglund, P. & Brodin, P. Current perspectives of natural killer cell education by MHC class I molecules. Nat Rev Immunol 10, 724–734, https://doi.org/10.1038/nri2835 (2010).