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