The adaptor protein CARD9 is essential for the activation of myeloid cells through ITAM-associated and Toll-like receptors

Hiromitsu Hara, Chitose Ishihara, Arata Takeuchi, Takayuki Imanishi, Liquan Xue, Stephan W. Morris, Masanori Inui, Toshiyuki Takai, Akira Shibuya, Shinobu Saijo, Yoichiro Iwakura, Naohito Ohno, Haruhiko Koseki, Hiroki Yoshida, Josef M. Penninger, Takashi Saito

Research output: Contribution to journalArticlepeer-review

228 Citations (Scopus)

Abstract

Immunoreceptor tyrosine-based activation motifs (ITAMs) are crucial in antigen receptor signaling in acquired immunity. Although receptors associated with the ITAM-bearing adaptors FcRγ 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-κB 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-κB 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.

Original languageEnglish
Pages (from-to)619-629
Number of pages11
JournalNature Immunology
Volume8
Issue number6
DOIs
Publication statusPublished - 2007 Jun

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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