大酶K调解了依赖IL-23的炎症和皮病中的角质细胞增殖
Katlyn C Richardson1,2,3, Alexandre Aubert1,2,3, Christopher T Turner1,2,3
1International Collaboration on Repair Discoveries (ICORD) Centre, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, BC, Canada.
Frontiers in immunology
|June 21, 2024
概括
大酶K (GzmK) 通过促进IL-23分泌和皮肤细胞增殖,加剧牛皮. 在小鼠中降低GzmK水平显著减轻了牛皮的症状,强调GzmK是这种炎症性皮肤疾病的潜在治疗标.
科学领域:
- 免疫皮肤学 免疫皮肤学
- 分子生物学分子生物学
- 炎症研究 炎症研究
背景情况:
- 牛皮是一种慢性炎症性皮肤疾病,其特点是IL-23/IL-17通路的激活.
- 酶K (GzmK) 是一种血清蛋白酶,与炎症性皮肤疾病有关.
研究的目的:
- 为了研究Granzyme K (GzmK) 在牛皮病的发病过程中的作用.
- 为了确定GzmK是否通过IL-23的产生和角质细胞的增殖,有助于牛皮的严重程度.
主要方法:
- 对人类牛皮病变与健康皮肤中的GzmK水平的分析.
- 使用小鼠模型的伊米基莫德 (IMQ) 诱导的牛皮来评估GzmK缺乏的小鼠的疾病严重程度.
- 在体外分子研究以阐明GzmK对巨细胞IL-23分泌和角质细胞增殖的影响.
主要成果:
- 与对照组相比,人类牛皮病变的GzmK水平显著更高.
- 缺乏GzmK的小鼠表现出牛皮的严重程度降低,包括延迟斑块形成,减少红血,减少表皮厚化.
- 在体外实验中证明了GzmK在增强巨细胞IL-23分泌和促进PAR-1-依赖的角质细胞增殖中的作用.
结论:
- 格兰酶K (GzmK) 在恶化牛皮方面发挥着重要作用.
- GzmK通过促进IL-23驱动的炎症和角质细胞的增殖,有助于牛皮的发病.
- 向Granzyme K (GzmK) 可能为治疗牛皮提供一种新的治疗策略.
相关概念视频
T Cell Types and Functions
999
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...
999
Renewal of Skin Epidermal Stem Cells
2.5K
The skin is divided into epidermis, dermis, and hypodermis, the skin's outermost, middle, and inner layers. The human epidermal layer regularly undergoes renewal, where old, dead cells are replaced by new cells. Epidermal stem cells or EpiSCs divide and differentiate to restore the lost cells. For the renewal process, some EpiSCs continuously self-renew. In contrast, few others differentiate into transit-amplifying cells, which later form prickle or spinous cells, followed by granular...
2.5K
The JAK-STAT Signaling Pathway
8.8K
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...
8.8K
Receptor Downregulation in MVBs
2.0K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.0K
Caspases
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
Cytoskeletal Linker Proteins - Plakins
2.3K
Plakins are large proteins with binding domains for microtubules, microfilaments, intermediate filaments, and membrane-associated protein complexes at cell junctions. Plakin functions are evolutionarily conserved and are primarily involved in organizing the different components of the cytoskeleton by crosslinking them to each other and connecting them to the cell-matrix and cell adhesion complexes. They are also known to interact with signal transducers, serve as scaffolds for signaling...
2.3K


