晚期内体/溶体功能降低通过慢性PI3k活动和SHP-1/SHIP-1缺陷促进SLE.
SunAh Kang1, Andrew J Monteith1, Liubov Arbeeva2
1Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, United States of America.
JCI insight
|February 17, 2026
概括
系统性红斑狼 (SLE) 患者表现出受损的晚期内和 lysosome (LEL) 酸化,导致细胞废物积累和免疫复合物的积累. 这种功能障碍可以作为特定类型的SLE疾病的生物标志物.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 病理生理学 病理生理学
背景情况:
- 细胞废物降解依赖于通过晚期内和溶酶体 (LEL) 酸化激活的酸酶.
- 功能障碍的LEL酸化与各种疾病有关.
研究的目的:
- 调查LEL酸化及其与系统性红斑狼 (SLE) 疾病活性和生物标志物的关联.
主要方法:
- 对SLE患者和小鼠模型 (MRL/lpr小鼠) 的横截面研究.
- 对LEL酸化,表面结合核细胞和IgG-免疫复合体 (IgG-IC) 积累的分析.
- 研究了涉及PI3k,SHP-1和SHIP-1的机制性途径.
主要成果:
- 在SLE患者中,LEL酸化降低,免疫细胞表面核细胞积累增加.
- 活跃的SLE与受损的LEL酸性和IgG-IC外细胞形成有关.
- 小鼠模型和特定分子缺陷 (SHP-1,SHIP-1) 重复了LEL功能障碍.
- 非酸性LEL在67%的SLE患者中被发现,并与特定的临床表现 (关节炎,皮疹,炎) 相联系.
结论:
- 低位位功能障碍是SLE的常见发现,与活跃的疾病和特定的临床特征有关.
- 较小位功能障碍可能代表SLE的一个独特的内型.
- 较小位的功能障碍有可能成为SLE患者分层的有价值生物标志物.
相关概念视频
The JAK-STAT Signaling Pathway
13.2K
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...
13.2K
The Early Endosome: Endocytosis of Transferrin
4.9K
Essential proteins such as insulin or low-density lipoprotein (LDL) and micronutrients such as iron enter a eukaryotic cell through receptor-mediated endocytosis. Subsequently, the early endosomes fuse with the vesicles containing such receptor-ligand complexes and play a vital role in sorting the incoming ligands and receptors. While the ligands are either degraded inside the vesicle or released into the cytosol, their receptors are returned to the plasma membrane for further rounds of...
4.9K
Lysosomal Hydrolases
4.7K
Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
4.7K
PI3K/mTOR/AKT Signaling Pathway
5.7K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
5.7K
Phosphoinositides and PIPs
10.3K
Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
10.3K
Abnormal Proliferation
5.3K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.3K


