LLT1‐mediated Activation of IFN‐γ Production in Human Natural Killer Cells Involves ERK Signalling Pathway
N. D. Bambard, S. Mathew, P. A. Mathew
Mar 1, 2010
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21
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Journal
Scandinavian Journal of Immunology
Full text
Semantic Scholar
Key Takeaway Key Takeaway: LLT1-mediated IFN production in human NK cells involves the ERK signaling pathway, but not PKC, PI3K, or calcineurin, suggesting post-transcriptional or translational events.
Abstract
Natural killer (NK) cell functions are regulated by a delicate balance of signals received through activating and inhibitory receptors expressed on the cell surface. Lectin‐like transcript‐1 (LLT1), expressed on a subpopulation of NK cells and other immune cells is a ligand for the NK cell inhibitory receptor, NKR‐P1A (CD161). Previous studies showed that cross‐linking surface LLT1 with a monoclonal antibody stimulated NK cell IFN‐γ secretion but had no effect on cytotoxicity. Here, we have examined the signalling pathways associated with LLT1‐stimulated IFN‐γ secretion. We ligated LLT1 on NK92 cells with CD161 on target cells and analysed IFN‐γ production in the presence of pharmacological inhibitors specific for various signalling mechanisms. These results indicate that LLT1 employs Src‐PTK, p38 and ERK signalling pathways, but not PKC, PI3K or calcineurin. Phosphorylation studies of the signalling adaptor molecules confirmed that the ERK signalling pathway is associated with LLT1‐mediated IFN‐γ production. LLT1 ligation is not associated with any change in detectable IFN‐γ mRNA levels suggesting that LLT1‐stimulated IFN‐γ production in NK cells may involve post‐transcriptional or translational events.