c-CBL/LCK/c-JUN/ETS1/CD28轴通过抑制Th2分化来抑制儿童喘
1Department of Pediatrics, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, 110004, China.
Molecular medicine (Cambridge, Mass.)
|September 28, 2024
概括
卡西塔斯B系淋巴瘤 (c-CBL) 在患有喘的儿童中被发现是下调的. 通过向LCK/c-JUN/CD28通路,恢复c-CBL水平缓解了喘症状,并抑制了2型炎症.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 儿科 儿科 儿科
背景情况:
- 喘是一种普遍的儿童免疫疾病,由2型炎症驱动.
- 辅助性T2 (Th2) 细胞是这种炎症的关键媒介,它们的过度活化与喘恶化有关.
- 在患有喘的儿童中,观察到CD4+T细胞中卡西塔斯B系淋巴瘤 (c-CBL) 表达的减少.
研究的目的:
- 调查c-CBL在儿童喘中的作用.
- 探索c-CBL对Th2细胞分化的影响.
- 阐明涉及c-CBL在喘发病过程中的潜在分子机制.
主要方法:
- 从喘儿童和健康对照组收集了周围血液,以评估CD4+T细胞中的c-CBL表达.
- 建立了由卵胺 (OVA) 诱导的喘小鼠模型,以测量c-CBL水平.
- 使用了 in vitro 功能增益实验和 in vivo 在喘小鼠中c-CBL的lentiviral 输送.
主要成果:
- 与对照人群相比,喘儿童和小鼠的CD4+T细胞中c-CBL表达显着较低.
- 在实验性喘中,c-CBL过度表达减少了肺病理和2型炎症.
- c-CBL通过促进激活c-JUN的激酶LCK的泛基化来抑制Th2分化,随后影响CD28表达.
结论:
- c-CBL通过c-CBL/LCK/c-JUN/ETS1/CD28通路缓解喘并抑制Th2分化的作用.
- 这一途径为儿童喘提供了潜在的新型治疗点.
- 这些发现突显了c-CBL在喘病因发生中的保护作用.
相关概念视频
T Cell Types and Functions
959
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...
959
Asthma-II: Pathophysiology and Classification
2.6K
Asthma is a prevalent chronic respiratory condition marked by inflammation and hyperresponsiveness of the airways. Its pathophysiology involves complex interactions among inflammatory pathways, immune responses, and neural mechanisms.
Additionally, environmental and genetic factors play crucial roles in determining an individual's susceptibility to asthma and the severity of their condition.
Critical processes in asthma pathophysiology include:
Additionally, environmental and genetic factors play crucial roles in determining an individual's susceptibility to asthma and the severity of their condition.
Critical processes in asthma pathophysiology include:
2.6K
Antiasthma Drugs: Mast Cell Stabilizers and Anti-IgE Drugs
241
Asthma is a chronic respiratory condition for which new therapeutic avenues, including anti-inflammatory drugs like mast cell stabilizers and anti-IgE treatments, continue to be developed.
Mast cell stabilizers, such as cromolyn (also known as sodium cromoglycate) and nedocromil (Tilade), are effective drugs in asthma management. These stabilizers hinder histamine release by skillfully obstructing the activation of mast cells and other cellular entities. Notably, they navigate this task without...
Mast cell stabilizers, such as cromolyn (also known as sodium cromoglycate) and nedocromil (Tilade), are effective drugs in asthma management. These stabilizers hinder histamine release by skillfully obstructing the activation of mast cells and other cellular entities. Notably, they navigate this task without...
241
The JAK-STAT Signaling Pathway
8.7K
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...
8.7K
Drugs Used in Lower Respiratory Disorders: Overview
358
Lower respiratory tract disorders present challenges that often require skilled and nuanced approaches for effective management. Common ailments, such as asthma and chronic obstructive pulmonary disease (COPD), have prompted the development of intricate treatment strategies involving bronchodilators and anti-inflammatory drugs, each tailored to ease breathing and revitalize the lungs.
Bronchodilators, the first step of respiration enhancement, come in various forms, each with its own mechanism...
Bronchodilators, the first step of respiration enhancement, come in various forms, each with its own mechanism...
358
Antiasthma Drugs: Inhaled Corticosteroids and Glucocorticoids
226
Inhaled corticosteroids (ICS) are anti-inflammatory drugs used primarily in treating persistent asthma and providing long-term maintenance. They target the bronchial mucosa, the lining of the airways, to control inflammation, a critical factor in asthma progression and exacerbation.
ICS work through a multifaceted mechanism of action. They suppress the inflammatory response caused by the proliferation of TH cells. They also reduce the transcription of the IL-2 gene, which is involved in the...
ICS work through a multifaceted mechanism of action. They suppress the inflammatory response caused by the proliferation of TH cells. They also reduce the transcription of the IL-2 gene, which is involved in the...
226


