| First Author | Hara H | Year | 2007 |
| Journal | Nat Immunol | Volume | 8 |
| Issue | 6 | Pages | 619-29 |
| PubMed ID | 17486093 | Mgi Jnum | J:122394 |
| Mgi Id | MGI:3714228 | Doi | 10.1038/ni1466 |
| Citation | Hara H, et al. (2007) The adaptor protein CARD9 is essential for the activation of myeloid cells through ITAM-associated and Toll-like receptors. Nat Immunol 8(6):619-29 |
| abstractText | Immunoreceptor tyrosine-based activation motifs (ITAMs) are crucial in antigen receptor signaling in acquired immunity. Although receptors associated with the ITAM-bearing adaptors FcRgamma 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-kappaB 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-kappaB 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. |
