写的:
SVP and Head of Research and Early Development, 呼吸与免疫学, AstraZeneca
Executive Director and Head of Bioscience Asthma and Skin Immunity, AstraZeneca
The interleukin 33 (IL-33) protein is a key regulator of immune response and tissue remodelling in chronic inflammatory diseases such as chronic obstructive pulmonary disease (慢性阻塞性肺病), 哮喘和糖尿病肾病, 以及COVID-19等急性呼吸道感染. 它通过两种不同的信号机制发挥作用, 其中一个是最近才被发现的.
为了保护澳门第一赌城在线娱乐不生病, our immune system needs to detect and respond to a wide range of signals and triggers. 然而,, while the acute responses of our immune system are vital for survival, extreme or persistent immune activation can become harmful and contributes to disease progression in various chronic illnesses including chronic obstructive pulmonary disease (慢性阻塞性肺病), 哮喘, 特应性皮炎和糖尿病肾病. 这些疾病影响了6亿多人1慢性阻塞性肺病是全球第三大死亡原因2. By understanding the science behind these diseases we’re exploring new ways to stop their progression, 达到缓解并最终治愈它们.
也被称为警报, IL-33 is best known as a protein that acts as a cytokine to trigger a response from the immune system. It is found constitutively in the nucleus of numerous types of cell throughout the body including the lungs and skin. 当这些细胞受损或坏死时, IL-33 is released and is able to interact with cells from the immune system. 它作用于包括中性粒细胞在内的一系列细胞, 先天淋巴样细胞, Th2细胞, 嗜酸性粒细胞和肥大细胞通过一种叫做ST2的受体蛋白. IL-33 binding to ST2 triggers responses that lead to inflammation.
IL-33在组织重构中的作用
The form of IL-33 that exists inside cells and causes inflammation is known as reduced IL-33. Once released from cells, IL-33 is quickly converted into an oxidised form. Oxidised IL-33 doesn’t interact with ST2 and cannot cause inflammation, 所以IL-33的转换限制了它的作用范围.
Oxidised IL-33 has another role, however, which has recently been discovered. Oxidised IL-33 interacts with a different set of receptor proteins on the surface of epithelial cells3, the cells that form surfaces such as the linings of the airways in our lungs. 在这个角色中, IL-33 can trigger tissue remodelling changing how cells organise and specialise to perform different roles.
通过RAGE/EGFR和ST2途径氧化IL-33信号3,4
IL-33在慢性疾病中的作用
Our research has helped to show that IL-33 has a key role in several major illnesses and it is an attractive target for developing therapies.
Hallmarks of chronic lung diseases include changes to the cells that line the airways of the lungs, 这包括产生粘液的高脚杯细胞增加, 这反过来又会导致粘液分泌过剩. Oxidised IL-33 may be a driver of the mucus overproduction that we see in 慢性阻塞性肺病
Oxidised IL-33 may be a driver of the mucus overproduction in 慢性阻塞性肺病3
We are also working towards identification of patient subpopulations that may be particularly responsive to therapies that target IL-33, allowing for a precision medicine-led approach to treating these cases. Work is ongoing to uncover a suitable clinical test that can reliably identify these patients so that they can be matched to precision medicines which they are most likely to benefit from
复杂疾病的挑战
Chronic diseases are difficult to treat and manage because they are highly heterogeneous, varying between patients as well as over time and in response to a wide range of external factors. There is still a huge amount we do not understand about these illnesses but, 通过遵循科学, we are learning more about the pathogenesis and uncovering new targets to help manage and ultimately cure these diseases.
