期刊
NATURE IMMUNOLOGY
卷 8, 期 6, 页码 619-629出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ni1466
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- NCI NIH HHS [CA21765, R01 CA87064] Funding Source: Medline
Immunoreceptor tyrosine-based activation motifs (ITAMs) are crucial in antigen receptor signaling in acquired immunity. Although receptors associated with the ITAM-bearing adaptors FcRc and DAP12 on myeloid cells have been suggested to activate innate immune responses, the mechanism coupling those receptors to 'downstream' signaling events is unclear. The CARMA1-Bcl-10-MALT1 complex is critical for the activation of transcription factor NF-kappa B in lymphocytes but has an unclear function in myeloid cells. Here we report that deletion of the gene encoding the Bcl-10 adaptor-binding partner CARD9 resulted in impaired myeloid cell activation of NF-kappa B signaling by several ITAM-associated receptors. Moreover, CARD9 was required for Toll-like receptor-induced activation of dendritic cells through the activation of mitogen-activated protein kinases. Although Bcl10(-/-) and Card9(-/-) mice had similar signaling impairment in myeloid cells, Card11(-/-) (CARMA1-deficient) myeloid cell responses were normal, and although Card11(-/-) lymphocytes were defective in antigen receptor-mediated activation, Card9(-/-) lymphocytes were not. Thus, the activation of lymphoid and myeloid cells through ITAM-associated receptors or Toll-like receptors is regulated by CARMA1-Bcl-10 and CARD9-Bcl-10, respectively.
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