通过促进ILC2s中的CGRP信号传递,PAC1抑制了2型炎症
Yuan Jin1, Bowen Liu1,2, Qiuyu Li3
1Institute of Systems Biomedicine, Department of Pathology, Beijing Key Laboratory of Tumor Systems Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
The Journal of clinical investigation
|September 17, 2024
概括
激活细胞的酶1 (PAC1) 调节2组先天性淋巴细胞 (ILC2s) 对神经信号的反应. 缺少PAC1会使过敏性气道炎症恶化,这表明PAC1是2型炎症疾病的治疗点.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 神经科学是一个神经科学.
背景情况:
- 2组先天性淋巴细胞 (ILC2s) 在2型炎症中至关重要,神经信号成为关键调节者.
- 通过ILC2s调节它们对神经信号的反应的内在机制尚不清楚.
研究的目的:
- 研究激活细胞1 (PAC1) 酸酶在调节ILC2对神经信号传递的反应中的作用.
- 探索PAC1作为2型炎症相关疾病的治疗点的潜力.
主要方法:
- 单细胞RNA测序 (scRNA-Seq) 用于识别ILC2s中的免疫调节分子.
- 在ILC2s中对PAC1进行基因切除,以评估其功能影响.
- 过敏呼吸道炎症的体内小鼠模型 (使用Alternaria alternata或papain).
- 对人类循环中的ILC2s进行分析,以将PAC1表达与细胞数量和IL-13水平相关联.
主要成果:
- 发现PAC1可选择性地增强ILC2s中的素基因相关 (CGRP) 信号传递,以细胞内在的方式.
- 在ILC2s中PAC1的遗传删除减少了CGRP对增殖和IL-13分泌的抑制作用.
- 在小鼠模型中,PAC1缺乏会加剧过敏性气道炎症.
- 在人类ILC2s中,PAC1表达与ILC2数量和IL-13表达相反相关.
- PAC1影响染色体的可访问性,这对于CGRP反应基因表达至关重要.
结论:
- PAC1是ILC2对神经信号,特别是CGRP的反应的关键调节者.
- PAC1在调节过敏性气道炎症方面发挥着重要作用.
- PAC1代表了一种有前途的治疗点,用于治疗2型炎症相关疾病,如喘和肺纤维化.
相关概念视频
T Cell Types and Functions
960
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...
960
GPCRs Regulate Adenylyl Cylase Activity
5.3K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
5.3K
IP3/DAG Signaling Pathway
11.9K
Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
11.9K
Inflammatory Response
1.9K
An inflammatory response is a localized, nonspecific immune reaction that occurs when a tissue is injured. It is characterized by redness, swelling, heat, and pain, which are commonly called the cardinal signs and symptoms of inflammation. Inflammation can sometimes result in a loss of function.
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
1.9K
Role Of Notch Signalling In Intestinal Stem Cell Renewal
2.1K
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.1K
Inflammatory Bowel Disease II: Crohn's Disease
200
Introduction
Inflammatory bowel disease, commonly known as IBD, refers to a collection of disorders that lead to persistent inflammation of the gastrointestinal tract. The two types of IBD are ulcerative colitis, which impacts the colon, and Crohn's disease, which can involve any part of the gastrointestinal segment.
Crohn's disease
Crohn's disease is a chronic, systemic inflammatory bowel disease (IBD) that predominantly affects the gastrointestinal tract. It is marked by...
Inflammatory bowel disease, commonly known as IBD, refers to a collection of disorders that lead to persistent inflammation of the gastrointestinal tract. The two types of IBD are ulcerative colitis, which impacts the colon, and Crohn's disease, which can involve any part of the gastrointestinal segment.
Crohn's disease
Crohn's disease is a chronic, systemic inflammatory bowel disease (IBD) that predominantly affects the gastrointestinal tract. It is marked by...
200


