Bcl10 plays a divergent role in NK cell-mediated cytotoxicity and cytokine generation
| Autor: | Snjezana Kutlesa, Renren Wen, Subramaniam Malarkannan, Jeyarani Regunathan, Demin Wang, Hu Zeng, Yuhong Chen, Haiyan Chu |
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| Rok vydání: | 2007 |
| Předmět: |
Cytotoxicity
Immunologic Immunology CHO Cells Biology Natural killer cell Interleukin 21 Mice Cricetulus Cell Line Tumor Cricetinae medicine Immunology and Allergy CXCL10 Animals Antigens Ly Lectins C-Type Receptors Immunologic CXCL14 Adaptor Proteins Signal Transducing Mice Knockout Cell Differentiation NKG2D B-Cell CLL-Lymphoma 10 Protein Immunity Innate Cell biology Killer Cells Natural Mice Inbred C57BL medicine.anatomical_structure Self Tolerance NK Cell Lectin-Like Receptor Subfamily K Antigens Surface Cancer research Interleukin 12 XCL2 Cytokines Interleukin-2 Receptors Natural Killer Cell NK Cell Lectin-Like Receptor Subfamily B Chemokines NK Cell Lectin-Like Receptor Subfamily A Receptors NK Cell Lectin-Like |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 179(6) |
| ISSN: | 0022-1767 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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