Abstract
The 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 vivo administration 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.
Highlights
The contribution of natural killer (NK) cells to the clearance of hepatic viral infections is well recognized
We recently demonstrated that αGalCerMPEG-activated Invariant natural killer T (iNKT) cells affect splenic NK cell differentiation and stimulate mainly educated NK cells, thereby highlighting the potential of the iNKT-NK cell axis as a target for immune interventions
We addressed whether iNKT cell stimulation can beneficially modulate liver NK cells with a special focus on their functionality, differentiation status and migratory capacities
Summary
The contribution of natural killer (NK) cells to the clearance of hepatic viral infections is well recognized. Natural killer (NK) cells belong to the innate lymphocyte population and represent an essential component of the first line of defense against virally infected and transformed cells[1]. They exert regulatory functions by secreting a variety of cytokines critical for innate and adaptive immune responses[2,3,4]. New insights into the mechanisms controlling NK cell functionality emphasize their heterogeneity and render them potential targets for immune interventions[5,6,7]. NK cells expressing both CD27 and Mac-1 display a low activation threshold and account for the most functional subset holding the highest cytotoxic and cytokine secreting potential. The liver contains the highest percentage of NK cells
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