【博士論文】学術データベース

博士論文 / Intracellular metabolite β-glucosylceramide is an endogenous Mincle ligand possessing immunostimulatory activity 細胞内代謝物である β-glucosylceramideは免疫活性化能を有するMincleの内因性リガンドである

著者

書誌事項

タイトル

Intracellular metabolite β-glucosylceramide is an endogenous Mincle ligand possessing immunostimulatory activity

タイトル別名

細胞内代謝物である β-glucosylceramideは免疫活性化能を有するMincleの内因性リガンドである

著者名

永田雅大

学位授与大学

九州大学 (大学ID:0069) (CAT機関ID:KI000822)

取得学位

博士(医学)

学位授与番号

甲第13653号

学位授与年月日

2017-06-30

注記・抄録

Sensing and reacting to tissue damage is a fundamental function of immune systems. Macrophage inducible C-type lectin (Mincle) is an activating C-type lectin receptor that senses damaged cells. Notably, Mincle also recognizes glycolipid ligands on pathogens. To elucidate endogenous glycolipids ligands derived from damaged cells, we fractionated supernatants from damaged cells and identified a lipophilic component that activates reporter cells expressing Mincle. Mass spectrometry and NMR spectroscopy identified the component structure as β-glucosylceramide (GlcCer), which is a ubiquitous intracellular metabolite. Synthetic β-GlcCer activated myeloid cells and induced production of inflammatory cytokines; this production was abrogated in Mincle-deficient cells. Sterile inflammation induced by excessive cell death in the thymus was exacerbated by hematopoietic-specific deletion of degrading enzyme of β-GlcCer (β-glucosylceramidase, GBA1). However, this enhanced inflammation was ameliorated in a Mincle-deficient background. GBA1-deficient dendritic cells (DCs) in which β-GlcCer accumulates triggered antigen-specific T-cell responses more efficiently than WT DCs, whereas these responses were compromised in DCs from GBA1 × Mincle double-deficient mice. These results suggest that β-GlcCer is an endogenous ligand for Mincle and possesses immunostimulatory activity.

PubMed番号 : info:pmid/28373578

目次

  1. 2018-03-04 再収集 / (med3035.pdf)
  2. 2018-03-04 再収集 / (med3035_abstract.pdf)
  3. 2018-03-04 再収集 / (med3035_review.pdf)

各種コード

NII論文ID(NAID)

500001049246

NII著者ID(NRID)
  • 8000001165686
DOI (出版社)

10.1073/pnas.1618133114

本文言語コード

eng

データ提供元

機関リポジトリ / NDLデジタルコレクション

博士論文 / 九州大学 / 医学

博士論文 / 九州大学

博士論文 / 医学

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