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Cutting Edge: Murine NK Cells Degranulate and Retain Cytotoxic Function without Store-Operated Calcium Entry.


ABSTRACT: Sustained Ca2+ signaling, known as store-operated calcium entry (SOCE), occurs downstream of immunoreceptor engagement and is critical for cytotoxic lymphocyte signaling and effector function. CD8+ T cells require sustained Ca2+ signaling for inflammatory cytokine production and the killing of target cells; however, much less is known about its role in NK cells. In this study, we use mice deficient in stromal interacting molecules 1 and 2, which are required for SOCE, to examine the contribution of sustained Ca2+ signaling to murine NK cell function. Surprisingly, we found that, although SOCE is required for NK cell IFN-? production in an NFAT-dependent manner, NK cell degranulation/cytotoxicity and tumor rejection in vivo remained intact in the absence of sustained Ca2+ signaling. Our data suggest that mouse NK cells use different signaling mechanisms for cytotoxicity compared with other cytotoxic lymphocytes.

SUBMITTER: Freund-Brown J 

PROVIDER: S-EPMC5807242 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Cutting Edge: Murine NK Cells Degranulate and Retain Cytotoxic Function without Store-Operated Calcium Entry.

Freund-Brown Jacquelyn J   Choa Ruth R   Singh Brenal K BK   Robertson Tanner Ford TF   Ferry Gabrielle M GM   Viver Eric E   Bassiri Hamid H   Burkhardt Janis K JK   Kambayashi Taku T  

Journal of immunology (Baltimore, Md. : 1950) 20170809


Sustained Ca<sup>2+</sup> signaling, known as store-operated calcium entry (SOCE), occurs downstream of immunoreceptor engagement and is critical for cytotoxic lymphocyte signaling and effector function. CD8<sup>+</sup> T cells require sustained Ca<sup>2+</sup> signaling for inflammatory cytokine production and the killing of target cells; however, much less is known about its role in NK cells. In this study, we use mice deficient in stromal interacting molecules 1 and 2, which are required for  ...[more]

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