NK-activating dendritic cells are elicited by stimulation with Toll-like receptor 3
- フォーマット:
- 論文
- 責任表示:
- Seya, Tsukasa ; Matsumoto, Misako ; Ebihara, Takashi ; Akazawa, Takashi
- 言語:
- 英語
- 出版情報:
- 弘前大学大学院医学研究科・弘前医学会, 2007-11-29
- 著者名:
- 掲載情報:
- 弘前医学
- ISSN:
- 0439-1721
- 巻:
- 59
- 通号:
- Supplement
- 開始ページ:
- S43
- 終了ページ:
- S51
- バージョン:
- publisher
- 概要:
- Double-stranded (ds)RNA-recognition receptors reside in the cytoplasm and membranes of cells. Thesereceptors are implicated in the differential screening of microbes by the host. Myeloid dendritic cells (mDCs)recognize and respond to polyI: … C, an analog of dsRNA, by endosomal TLR3 and cytoplasmic MDA5. NK cells areinduced in vivo by the administration of polyI:C to mice and in vitro are reciprocally activated by mDCs, although themolecular mechanisms as yet undetermined. Here, we show that the TLR adapter TICAM-1 (TRIF) participates inmDC-derived antitumor NK activation. In a syngeneic mouse tumor implant model, intraperitoneal administration ofpolyI:C led to the retardation of tumor growth, which eff ect relied largely on NK activation. This NK-dependent tumorregression did not occur in TICAM-1-/- or IFNAR-/- mice, while a normal NK antitumor response was induced in PKR-/-,MyD88-/-, IFN-β-/- and wild-type mice. IFNAR was a prerequisite for the induction of IFN-α/β and TLR3. The lackof TICAM-1 did not aff ect IFN production but resulted in unresponsiveness to IL-12 production, mDC maturation andpolyI:C-mediated antitumor activity. This NK activation required NK-mDC contact in in vitro transwell analysis. NKantitumoractivity was successfully introduced into tumor-implanted mice by transferring mDCs expressing TICAM-1.Implanted tumor growth in IFNAR-/- mice was retarded by adoptively transferring polyI:C-treated TICACM-1-positivemDCs but not TICAM-1-/- mDCs. Thus, TICAM-1 rather than MDA5 in mDCs critically facilitated mDC-NK contactand activation of antitumor NK, resulting in the regression of low MHC-expressing tumors 続きを見る
- URL:
- http://hdl.handle.net/10129/2215
類似資料:
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