Bcl10 plays a divergent role in NK cell-mediated cytotoxicity and cytokine generation

Subramaniam Malarkannan, Jeyarani Regunathan, Haiyan Chu, Snjezana Kutlesa, Yuhong Chen, Hu Zeng, Renren Wen, Demin Wang

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Activating receptors such as NKG2D and Ly49D mediate a multitude of effector functions including cytotoxicity and cytokine generation in NK cells. However, specific signaling events that are responsible for the divergence of distinct effector functions have yet to be determined. In this study, we show that lack of caspase recruitment domain-containing protein Bcl10 significantly affected receptor-mediated cytokine and chemokine generation, but not cytotoxicity against tumor cells representing "missing-self" or "induced-self." Lack of Bcl10 completely abrogated the generation of GM-CSF and chemokines and it significantly reduced the generation of IFN-γ(>75%) in NK cells. Commitment, development, and terminal maturation of NK cells were largely unaffected in the absence of Bcl10. Although IL-2-activated NK cells could mediate cytotoxicity to the full extent, the ability of the freshly isolated NK cells to mediate cytotoxicity was somewhat reduced. Therefore, we conclude that the Carma1-Bcl10-Malt1 signaling axis is critical for cytokine and chemokine generation, although it is dispensable for cytotoxic granule release depending on the activation state of NK cells. These results indicate that Bcl10 represents an exclusive "molecular switch" that links the upstream receptor-mediated signaling to cytokine and chemokine generations.

Original languageEnglish (US)
Pages (from-to)3752-3762
Number of pages11
JournalJournal of Immunology
Volume179
Issue number6
DOIs
StatePublished - Sep 15 2007

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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