Dectin-1 intracellular domain determines species-specific ligand spectrum by modulating receptor sensitivity

• Material Type: 博士論文
• Title: Dectin-1 intracellular domain determines species-specific ligand spectrum by modulating receptor sensitivity
• Author/Editor: 髙野, 智嗣
• Author Heading: 髙野, 智嗣
• Publication Date: 2018-03-31
• Publication Date (W3CDTF): 2018-03-31
• Alternative Title: Dectin-1による種特異的リガンド認識特性の決定機構に関する研究
• Contributor: 林, 哲也; 馬場, 義裕; 小野, 悦郎
• Degree grantor/type: 九州大学
• Date Granted: 2018-03-31
• Date Granted (W3CDTF): 2018-03-31
• Dissertation Number: 甲第13971号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第13971号
• Text Language Code: eng
• Target Audience: 一般
• Note (General): C-type lectin receptors (CLRs) comprise a large family of immunoreceptors that recognize polysaccharide ligands exposed on pathogen surfaces and are conserved among mammals. However, interspecies differences in their ligand spectrums are not fully understood. Dectin-1 is a well-characterized CLR that recognizes β-glucan. We report here that seaweed-derived fucan activates cells expressing human Dectin-1 but not mouse Dectin-1. Low-valency β-glucan components within fucan appeared to be responsible for this activation, as the ligand activity was eliminated by β-glucanase treatment. The low-valency β-glucan laminarin also acted as an agonist for human Dectin-1 but not for mouse Dectin-1, whereas the high-valency β-glucan curdlan activated both human and mouse Dectin-1. Reciprocal mutagenesis analysis revealed that the ligand-binding domain of human Dectin-1 does not determine its unique sensitivity to low-valency β-glucan. Rather, we found that its intracellular domain renders human Dectin-1 reactive to low-valency β-glucan ligand. Substitution with two amino acids, Glu^2 and Pro^5, located in the human Dectin-1 intracellular domain was sufficient to confer sensitivity to low-valency β-glucan in mouse Dectin-1. Conversely, the introduction of mouse-specific amino acids, Lys2 and Ser5, to human Dectin-1 reduced the reactivity to low-valency β-glucan. Indeed, low-valency ligands induced a set of proinflammatory genes in human but not mouse dendritic cells. These results suggest that the intracellular domain, not ligand-binding domain, of Dectin-1 determines the species-specific ligand profile.; PubMed番号 : 28848046
• DOI: 10.15017/1931824; https://doi.org/10.15017/1931824
• Persistent ID (NDL): info:ndljp/pid/11122692; https://dl.ndl.go.jp/pid/11122692
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2018-08-03T23:36:01+09:00
• Date Created (W3CDTF): 2018-05-30
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://dx.doi.org/10.15017/1931824; http://hdl.handle.net/2324/1931824
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp

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