First Author | Hidano S | Year | 2008 |
Journal | Int Immunol | Volume | 20 |
Issue | 3 | Pages | 345-52 |
PubMed ID | 18203684 | Mgi Jnum | J:131621 |
Mgi Id | MGI:3774071 | Doi | 10.1093/intimm/dxm150 |
Citation | Hidano S, et al. (2008) Distinct regulatory functions of SLP-76 and MIST in NK cell cytotoxicity and IFN-gamma production. Int Immunol 20(3):345-52 |
abstractText | Activation of NK cells is triggered by multiple receptors. We demonstrate here that SLP-76 is required for CD16- and NKG2D-mediated NK cell cytotoxicity, while MIST negatively regulates these responses in an SLP-76-dependent manner. Exceptionally, MIST acts as a positive regulator of cytotoxicity against YAC-1 cells, although SLP-76 plays a more key role. SLP-76 acts as a dominant positive regulator for both NKG2D-mediated and YAC-1 cell-triggered IFN-gamma production. Although NKG2D-mediated IFN-gamma production depends on phospholipase C (PLC) gamma 2, YAC-1 cell-triggered IFN-gamma production is PLC gamma 2- and Syk/ZAP-70 independent and nuclear factor-kappa B mediated. SLP-76 is required for this process in the presence of MIST but is dispensable in the absence of MIST. Thus, YAC-1 cell-triggered NKG2D-independent IFN-gamma production appears to be regulated by SLP-76-dependent and -independent pathways, in which the latter is negatively regulated by MIST. Taken together, these results suggest that SLP-76 and MIST distinctly but interactively regulate NK cell cytotoxicity and IFN-gamma production. |