相关实验视频
Updated: Jan 10, 2026

06:07
Measuring Mitochondrial Function of Naïve and Effector CD8 T Cells
Published on: March 28, 2025
966
免疫蛋白酶体通过调节线粒体容量来调节ILC2反应
Paôline Laurent1,2, Vidyanath Chaudhary1,2, Daqiang Li2
1Inflammation and Autoimmunity Program, Hospital for Special Surgery Research Institute, Hospital for Special Surgery, New York 10021, NY.
概括
免疫蛋白酶体 (i-20S) 选择性地控制2型先天性淋巴细胞 (ILC2s) 的线粒体功能. 抑制i-20S可逆地耗尽ILC2 ATP,防止激活并减轻气道炎症和喘.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 代谢途径 代谢途径
背景情况:
- 2型先天性淋巴细胞 (ILC2s) 对2型免疫至关重要.
- ILC2s与喘和呼吸道炎症等炎症状况有关.
- 免疫蛋白酶体 (i-20S) 已知可以降解蛋白质.
研究的目的:
- 研究免疫蛋白酶体 (i-20S) 在ILC2功能中的作用.
- 探索i-20S抑制对ILC2线粒体容量和新陈代谢的影响.
- 评估针对i-20S在2型炎症疾病中的治疗潜力.
主要方法:
- 对人类ILC2s (hILC2s) 中蛋白质酶子单元组成的分析.
- 在hILC2s中对i-20S (特别是β5i/LMP7) 的药理抑制以及线粒体功能,ROS产生,ATP水平和激活的评估.
- 在IL33诱导的呼吸道炎症和室内灰尘虫诱导的喘的小鼠模型中评估蛋白酶体抑制对ILC2s的影响.
主要成果:
- 人类ILC2s主要表达免疫- (β5i) 蛋白酶子单元.
- 在hILC2s中选择性i-20S抑制导致ROS的产生,抑制了akonitase,减少了ATP,并降低了ILC2的激活和细胞因子分泌,而不会导致细胞死亡.
- 在小鼠中,蛋白质酶抑制也类似地阻断了ILC2线粒体的功能和激活,有效地预防了气道炎症和喘.
结论:
- 免疫蛋白酶体 (i-20S) 对于维持ILC2线粒体功能和代谢状态至关重要.
- 选择性,可逆抑制i-20S提供了一个潜在的策略来调节类型2炎症疾病中的ILC2活性.
- 针对i-20S影响免疫细胞代谢,为喘等疾病提供了一种新的治疗方法.
相关概念视频
Translocation of Proteins into the Mitochondria
11.9K
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
11.9K
T Cell Types and Functions
2.1K
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...
2.1K
The Proteasome
1.6K
Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
1.6K
The Proteasome
10.0K
Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
10.0K
Mitochondrial Protein Sorting
5.6K
Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death. Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
5.6K
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

