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

Research output: Contribution to journalArticle

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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 1 2008
Externally publishedYes

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Natural Killer Cells
NF-kappa B
Type C Phospholipases

All Science Journal Classification (ASJC) codes

  • Immunology

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Distinct regulatory functions of SLP-76 and MIST in NK cell cytotoxicity and IFN-γ production. / Hidano, Shinya; Sasanuma, Hiroki; Ohshima, Keiko; Seino, Ken Ichiro; Kumar, Lalit; Hayashi, Katsuhiko; Hikida, Masaki; Kurosaki, Tomohiro; Taniguchi, Masaru; Geha, Raif S.; Kitamura, Daisuke; Goitsuka, Ryo.

In: International Immunology, Vol. 20, No. 3, 01.03.2008, p. 345-352.

Research output: Contribution to journalArticle

Hidano, S, Sasanuma, H, Ohshima, K, Seino, KI, Kumar, L, Hayashi, K, Hikida, M, Kurosaki, T, Taniguchi, M, Geha, RS, Kitamura, D & Goitsuka, R 2008, 'Distinct regulatory functions of SLP-76 and MIST in NK cell cytotoxicity and IFN-γ production', International Immunology, vol. 20, no. 3, pp. 345-352. https://doi.org/10.1093/intimm/dxm150
Hidano, Shinya ; Sasanuma, Hiroki ; Ohshima, Keiko ; Seino, Ken Ichiro ; Kumar, Lalit ; Hayashi, Katsuhiko ; Hikida, Masaki ; Kurosaki, Tomohiro ; Taniguchi, Masaru ; Geha, Raif S. ; Kitamura, Daisuke ; Goitsuka, Ryo. / Distinct regulatory functions of SLP-76 and MIST in NK cell cytotoxicity and IFN-γ production. In: International Immunology. 2008 ; Vol. 20, No. 3. pp. 345-352.
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