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白细胞介素33 (IL-33)蛋白是慢性炎症性疾病(如慢性阻塞性肺疾病(COPD))免疫反应和组织重塑的关键调节因子。, asthma and diabetic kidney disease, as well as acute respiratory infections such as COVID-19. It has its effects through two distinct signalling mechanisms, one of which has only recently been discovered.
In order to protect us from illness, 澳门葡京赌博游戏的免疫系统需要检测并对各种信号和触发因素做出反应. Yet, 而澳门葡京赌博游戏免疫系统的急性反应对生存至关重要, 极端或持续的免疫激活可能是有害的,并导致各种慢性疾病的疾病进展,包括慢性阻塞性肺疾病(COPD)。, asthma, atopic dermatitis and diabetic kidney disease. These illnesses affect over 600 million people1, with COPD being the third leading cause of death worldwide2. 通过了解这些疾病背后的科学,澳门葡京赌博游戏正在探索阻止疾病发展的新方法, achieve remission and eventually cure them.
Also known as an alarmin, IL-33是一种作为细胞因子触发免疫系统反应的蛋白质. 它组成部分存在于包括肺和皮肤在内的全身多种细胞的细胞核中. When these cells become damaged or die through necrosis, IL-33被释放并能够与免疫系统的细胞相互作用. It acts on a range of cells including neutrophils, innate lymphoid cells, Th2 cells, eosinophils and mast cells via a receptor protein called ST2. 与ST2结合的IL-33触发了导致炎症的反应.
IL-33 in tissue remodelling
存在于细胞内并引起炎症的IL-33的形式被称为减少IL-33. 一旦从细胞中释放出来,IL-33就会迅速转化为氧化形式. 氧化后的IL-33不与ST2相互作用,也不会引起炎症, so the conversion of IL-33 limits the range of its effect.
然而,氧化后的IL-33还有另一种作用,最近才被发现. 氧化的IL-33与上皮细胞表面的一组不同的受体蛋白相互作用3即形成表面的细胞,比如澳门葡京赌博游戏肺部的气道内壁. In this role, IL-33可以触发组织重塑,改变细胞如何组织和特化以执行不同的角色.
Oxidised IL-33 signals via RAGE/EGFR and ST2 pathways3,4
氧化的IL-33可能是COPD患者粘液过量产生的驱动因素3
澳门葡京赌博游戏也在努力确定可能对靶向IL-33的治疗有特别反应的患者亚群, 允许以精确医学为主导的方法来治疗这些病例. 目前正在开展工作,以发现一种合适的临床试验,能够可靠地识别这些患者,以便他们能够与最可能受益的精准药物相匹配
The challenge of complex diseases
慢性疾病难以治疗和管理,因为它们具有高度的异质性, 在不同的患者之间,随着时间的推移以及对各种外部因素的反应而变化. 澳门葡京赌博游戏对这些疾病还有很多不了解的地方,但是, by following the science, 澳门葡京赌博游戏正在更多地了解其发病机制,并发现新的靶点,以帮助管理和最终治愈这些疾病.