格兰酶K驱动一种新的强化补充激活路径
Carlos A Donado1,2, A Helena Jonsson1,3,2, Erin Theisen1,4
1Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.
bioRxiv : the preprint server for biology
|June 3, 2024
概括
在T细胞中发现的Granzyme K (GZMK) 激活了补充级联,独立于已知的途径. 这一发现揭示了一个新的机制,驱动着类风湿性关节炎等疾病的炎症.
科学领域:
- 免疫学 免疫学 免疫学
- 保护酶的功能 保护酶的功能
- 补充系统生物学 补充系统生物学
背景情况:
- 大酶是主要来自细胞毒性淋巴细胞的血清蛋白酶,它们以诱导细胞死亡而闻名.
- 新出现的证据表明,粒酶可以通过细胞外基质调节炎症.
- 格兰西姆K (GZMK) 在类风湿性关节炎等炎症组织中的CD8+T细胞中丰富,但其功能尚不清楚.
研究的目的:
- 阐明Grancyme K (GZMK) 在炎症情境中的功能.
- 调查GZMK在补充级联中的作用.
- 在类风湿性关节炎中识别GZMK介导的补充激活的细胞源和点.
主要方法:
- 生物化学试验评估GZMK对补充成分的蛋白质分解活性.
- 对补充级联激活产品的分析.
- 在类风湿性关节炎中对GZMK和补充成分进行免疫组织化学分析.
- 在炎症组织中识别产生补充蛋白的细胞类型.
主要成果:
- GZMK直接切割补充元件C2和C4,启动补充级联激活.
- 由GZMK驱动的激活产生C3和C5转化酶,导致过敏毒素,松素和膜攻击复合体.
- GZMK定位在RA突中的补充激活部位,纤维细胞是补充标的关键生产者.
- 这代表了一种新的,由淋巴细胞驱动的补体激活途径,独立于经典的,乳清蛋白或替代途径.
结论:
- GZMK启动了一个独特的补充激活路径,与既定路线不同.
- 这种GZMK介导的补充激活显著促进了类风湿性关节炎中的组织炎症.
- 这些发现表明,GZMK驱动的补充激活是各种慢性炎症疾病和感染的相关机制.
相关概念视频
01:27Complement System
2.3K
The complement system is a group of approximately 20 plasma proteins that strengthen the body's defenses against infections through opsonization, inflammation, and cell lysis. Opsonization involves coating pathogens with complement proteins, making them more recognizable and facilitating phagocyte engulfment. Certain complement proteins induce inflammation that attracts immune cells to the site of infection. Cell lysis involves the destruction of pathogens through the formation of a...
2.3K
01:17The Extrinsic Apoptotic Pathway
6.3K
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
6.3K
01:31The Intrinsic Apoptotic Pathway
6.5K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.5K
01:24Caspases
12.4K
Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
12.4K
01:30Apoptosis
11.4K
Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size...
11.4K
01:31Antigen Processing Pathways
996
MHC molecules are key players in the immune response, enabling T cells to recognize and respond to specific antigens. They are present on the surface of all nucleated cells in the body and are instrumental in presenting antigens to T cells and activating them. T cells recognize the MHC-antigen complex and initiate an immune response. MHC class I and MHC class II are two main types of MHC molecules, each associated with a distinct antigen processing pathway.
MHC Class I: Presenting Endogenous...
MHC Class I: Presenting Endogenous...
996