期刊
NATURE IMMUNOLOGY
卷 6, 期 6, 页码 579-586出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ni1204
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- NCI NIH HHS [R01 CA089294, CA89294] Funding Source: Medline
- NIDDK NIH HHS [R01 DK058066, DK58066] Funding Source: Medline
DAP12 is a signaling adaptor containing an immunoreceptor tyrosine-based activation motif (ITAM) that pairs with receptors on myeloid cells and natural killer cells. We examine here the responses of mice lacking DAP12 to stimulation through Toll-like receptors (TLRs). Unexpectedly, DAP12-deficient macrophages produced higher concentrations of inflammatory cytokines in response to a variety of pathogenic stimuli. Additionally, macrophages deficient in spleen tyrosine kinase (Syk), which signals downstream of DAP12, showed a phenotype identical to that of DAP12-deficient macrophages. DAP12-deficient mice were more susceptible to endotoxic shock and had enhanced resistance to infection by the intracellular bacterium Listeria monocytogenes. These data suggest that one or more DAP12-pairing receptors negatively regulate signaling through TLRs.
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