Distinct regulatory functions of SLP-76 and MIST in NK cell cytotoxicity and IFN-γ production

Shinya Hidano, Hiroki Sasanuma, Keiko Ohshima, Ken Ichiro Seino, Lalit Kumar, Katsuhiko Hayashi, Masaki Hikida, Tomohiro Kurosaki, Masaru Taniguchi, Raif S. Geha, Daisuke Kitamura, Ryo Goitsuka

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14 Citations (Scopus)

Abstract

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-γ production. Although NKG2D-mediated IFN-γ production depends on phospholipase C (PLC) γ2, YAC-1 cell-triggered IFN-γ production is PLCγ2- 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-γ 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-γ production.

Original languageEnglish
Pages (from-to)345-352
Number of pages8
JournalInternational immunology
Volume20
Issue number3
DOIs
Publication statusPublished - Mar 2008

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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    Hidano, S., Sasanuma, H., Ohshima, K., Seino, K. I., Kumar, L., Hayashi, K., Hikida, M., Kurosaki, T., Taniguchi, M., Geha, R. S., Kitamura, D., & Goitsuka, R. (2008). Distinct regulatory functions of SLP-76 and MIST in NK cell cytotoxicity and IFN-γ production. International immunology, 20(3), 345-352. https://doi.org/10.1093/intimm/dxm150