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Using expression profiling and gain\/loss-of-function analyses of mDC genes, we tried to identify a TICAM-1\u2013inducing 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\u2013dependent 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\u2013NK 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\u2013NK contact-mediated NK activation that is governed by a TLR signal-derived membrane molecule.<\/jats:p>","DOI":"10.1084\/jem.20091573","type":"journal-article","created":{"date-parts":[[2010,11,9]],"date-time":"2010-11-09T06:59:39Z","timestamp":1289285979000},"page":"2675-2687","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":85,"title":["Identification of a polyI:C-inducible membrane protein that participates in dendritic cell\u2013mediated natural killer cell activation"],"prefix":"10.1084","volume":"207","author":[{"given":"Takashi","family":"Ebihara","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo 060-8638, Japan 1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahiro","family":"Azuma","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo 060-8638, Japan 1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyuki","family":"Oshiumi","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo 060-8638, Japan 1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Kasamatsu","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo 060-8638, Japan 1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuya","family":"Iwabuchi","sequence":"additional","affiliation":[{"name":"Division of Immunobiology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan, 060-0815, Japan 2"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenji","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Allergy and Immunology, National Research Institute for Child Health and Development, Setagaya-ku, Tokyo 157-8535, Japan 3"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirohisa","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Allergy and Immunology, National Research Institute for Child Health and Development, Setagaya-ku, Tokyo 157-8535, Japan 3"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tadatsugu","family":"Taniguchi","sequence":"additional","affiliation":[{"name":"Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan 4"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Misako","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo 060-8638, Japan 1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsukasa","family":"Seya","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo 060-8638, Japan 1"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","published-online":{"date-parts":[[2010,11,8]]},"reference":[{"key":"2023072521542827700_bib1","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1073\/pnas.0605978104","article-title":"Antitumor NK activation induced by the Toll-like receptor 3-TICAM-1 (TRIF) pathway in myeloid dendritic cells","volume":"104","author":"Akazawa","year":"2007","journal-title":"Proc. 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