MyD88-IRF-7シグナリングの時空調節は,強力なタイプIインターフェロン誘導のためのシグナルです
Kenya Honda1, Yusuke Ohba, Hideyuki Yanai
1Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.
Nature
|April 9, 2005
まとめ
プラズマチトイド樹状細胞は,トール型受容体9 (TLR9) とMyD88-IRF-7シグナル伝達を通じてI型インターフェロン (IFN) を誘導する. これらの細胞におけるTLR9リガンドの内分体保持は,従来の樹状細胞とは異なり,強固なIFN誘導の鍵です.
科学分野:
- 免疫学 免疫学とは
- 細胞生物学 細胞生物学
- 分子生物学は分子生物学である.
背景:
- I型インターフェロン (IFN-alpha/beta) の誘導は,免疫にとって極めて重要です.
- プラズマサイトイド樹状細胞 (pDCs) は,IRF-7とMyD88.8.2に依存するIFN誘導のために,トール型受容体9 (TLR9) を利用する.
- pDCにおけるMyD88-IRF-7経路活性化の細胞型特異的メカニズムは不明である.
研究 の 目的:
- IFN誘導におけるMyD88-IRF-7信号伝達の時空調節を調査する.
- なぜpDCが,従来の樹状細胞 (cDC) ではないが,TLR9.9経由でIFNを強烈に誘導するかを理解するためです.
- TLR9媒介のIFN応答を調節するための治療戦略を探求する.
主な方法:
- pDCsとcDCsのエンドソームおよびリソームベシクル内のTLR9リガンド (CpG-A) の追跡.
- カチオン性脂質を用いたCpG-A局所化の操作.
- 操作されたTLR9リガンドプレゼンテーションに反応するIFN誘導経路の評価.
主要な成果:
- CpG-AはpDCsのMyD88-IRF-7と共にエンドソームに留まっていますが,cDCsのライソソームに急速に転送されます.
- 従来の樹状細胞は,CpG-Aがエンドソームに人工的に留まると,強力なIFN誘導を達成できます.
- エンドソーム保持は,cDCにおけるTLR9リガンドCpG-BによるIFN経路の活性化を可能にします.
結論:
- エンドソーム内のMyD88-IRF-7シグナル伝達の空間時間的制御は,TLR9媒介のIFN誘導レベルを決定する.
- TLR9リガンドに対するpDCとcDCの反応の決定的な要因は,エンドソーマの局所化である.
- エンドソーマのTLR9シグナル伝達をターゲットにすることで,免疫調節のための潜在的な治療アプローチが提供されます.
関連する概念動画
Regulation of the Unfolded Protein Response
2.9K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.9K
Immune Response Against Viral Pathogens
1.6K
The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
1.6K
T Cell Types and Functions
2.0K
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
2.0K
The JAK-STAT Signaling Pathway
11.7K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
11.7K
NF-κB-dependent Signaling Pathway
9.7K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
9.7K


