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Identification of a polyI:C-inducible membrane protein that participates in dendritic cell-mediated natural killer cell activation

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Title: Identification of a polyI:C-inducible membrane protein that participates in dendritic cell-mediated natural killer cell activation
Authors: Ebihara, Takashi Browse this author
Azuma, Masahiro Browse this author
Oshiumi, Hiroyuki Browse this author
Kasamatsu, Jun Browse this author
Iwabuchi, Kazuya Browse this author
Matsumoto, Kenji Browse this author
Saito, Hirohisa Browse this author
Taniguchi, Tadatsugu Browse this author
Matsumoto, Misako Browse this author
Seya, Tsukasa Browse this author
Issue Date: 8-Nov-2010
Publisher: Rockefeller University Press
Journal Title: Journal of Experimental Medicine
Volume: 207
Issue: 12
Start Page: 2675
End Page: 2687
Publisher DOI: 10.1084/jem.20091573
Abstract: In myeloid dendritic cells (mDCs), TLR3 is expressed in the endosomal membrane and interacts with the adaptor toll/interleukin 1 receptor homology domain-containing adaptor molecule 1 (TICAM-1; TRIF). TICAM-1 signals culminate in interferon (IFN) regulatory factor (IRF) 3 activation. Co-culture of mDC pretreated with the TLR3 ligand polyI:C and natural killer (NK) cells resulted in NK cell activation. This activation was triggered by cell-to-cell contact but not cytokines. Using expression profiling and gain/loss-of-function analyses of mDC genes, we tried to identify a TICAM-1-inducing membrane protein that participates in mDC-mediated NK activation. Of the nine candidates screened, one contained a tetraspanin-like sequence and satisfied the screening criteria. The protein, referred to as IRF-3-dependent NK-activating molecule (INAM), functioned in both the mDC and NK cell to facilitate NK activation. In the mDC, TICAM-1, IFN promoter stimulator 1, and IRF-3, but not IRF-7, were required for mDC-mediated NK activation. INAM was minimally expressed on NK cells, was up-regulated in response to polyI:C, and contributed to mDC-NK reciprocal activation via its cytoplasmic tail, which was crucial for the activation signal in NK cells. Adoptive transfer of INAM-expressing mDCs into mice implanted with NK-sensitive tumors caused NK-mediated tumor regression. We identify a new pathway for mDC-NK contact-mediated NK activation that is governed by a TLR signal-derived membrane molecule.
Rights: © 2010 Ebihara et al.
Type: article
URI: http://hdl.handle.net/2115/44721
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 瀬谷 司

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