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

International Immunology
Shinya HidanoRyo Goitsuka

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-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.

References

Jan 12, 1999·The Journal of Clinical Investigation·J L ClementsG A Koretzky
Jul 31, 1999·European Journal of Immunology·E J PetersonG A Koretzky
Nov 24, 1999·The Journal of Experimental Medicine·M Y CaoA Veillette
Aug 5, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·A HashimotoT Kurosaki
Jul 21, 2001·The Journal of Biological Chemistry·R GoitsukaD Kitamura
Feb 12, 2002·Nature Immunology·Francesco ColucciJames P Di Santo
Sep 3, 2002·Nature Immunology·Francesco ColucciPaul J Leibson
Nov 12, 2002·Nature Immunology·Susan GilfillanMarco Colonna
Jan 30, 2003·Nature Immunology·Martha S JordanGary A Koretzky
May 13, 2003·Nature Immunology·Daniel D BilladeauPaul J Leibson
Jun 6, 2003·Current Opinion in Immunology·Lewis L Lanier
Jun 17, 2004·Molecular and Cellular Biology·Oliver UttingAndré Veillette
Jul 9, 2004·The Journal of Experimental Medicine·Y Jeffrey ChiangRichard J Hodes
Sep 15, 2004·The Journal of Experimental Medicine·Marina CellaWojciech Swat
Nov 30, 2004·Science·Eric VivierFrédéric Vély
Jul 9, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ilaria TassiMarco Colonna
Nov 18, 2005·Blood·Sabrina ChiesaElena Tomasello

❮ Previous
Next ❯

Citations

Mar 23, 2013·Annual Review of Immunology·Eric O LongSumati Rajagopalan
Jun 1, 2016·Frontiers in Immunology·Kamalakannan RajasekaranSubramaniam Malarkannan
Dec 3, 2009·Immunopharmacology and Immunotoxicology·Takefumi InadaKoh Shingu
Sep 16, 2020·Journal of Leukocyte Biology·Claudia CantoniMassimo Vitale
Aug 9, 2016·PLoS Biology·Jacquelyn FreundTaku Kambayashi
Dec 10, 2009·Physiology·Yoshikazu Nakamura, Kiyoko Fukami
Feb 2, 2021·Journal of Diabetes and Metabolic Disorders·Suhaer Zeki Al-FadhelHussein Kadhem Al-Hakeim

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Biology: Molecular Imaging

Molecular imaging enables noninvasive imaging of key molecules that are crucial to tumor biology. Discover the latest research in molecular imaging in cancer biology in this feed.