Abstract:
Thymic stromal lymphopoietin (TSLP), is a protein belonging to a class of epithelial cytokines commonly called alarmins, which also includes IL-25 and IL-33. Functionally, TSLP is a key player in the immune response to environmental insults, initiating a number of downstream inflammatory pathways. TSLP performs its role by binding to a high-affinity heteromeric complex composed of the thymic stromal lymphopoietin receptor (TSLPR) chain and IL-7Rα. In recent years, the important role of proinflammatory cytokines in the etiopathogenesis of various chronic diseases such as asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), chronic obstructive pulmonary diseases (COPDs), and chronic spontaneous urticaria has been studied. Although alarmins have been found to be mainly implicated in the mechanisms of type 2 inflammation, studies on monoclonal antibodies against TSLP demonstrate partial efficacy even in patients whose inflammation is not definable as T2 and the so-called low T2. Tezepelumab is a human anti-TSLP antibody that prevents TSLP-TSLPR interactions. Several clinical trials are evaluating the safety and efficacy of Tezepelumab in various inflammatory disorders. In this review, we will highlight major recent advances in understanding the functional role of TSLP, its involvement in Th2-related diseases, and its suitability as a target for biological therapies.
摘要:
胸腺基质淋巴细胞生成素(TSLP),是一种蛋白质,属于一类通常称为alarmins的上皮细胞因子,其中还包括IL-25和IL-33。功能上,TSLP是对环境侮辱的免疫反应的关键参与者,启动一些下游炎症途径。TSLP通过与由胸腺基质淋巴细胞生成素受体(TSLPR)链和IL-7Rα组成的高亲和力异聚复合物结合而发挥作用。近年来,促炎细胞因子在各种慢性疾病如哮喘的发病机制中的重要作用,慢性鼻窦炎伴鼻息肉病(CRSwNP),慢性阻塞性肺疾病(COPDs),慢性自发性荨麻疹已被研究。尽管已发现警报主要与2型炎症的机制有关,针对TSLP的单克隆抗体的研究表明,即使在炎症不能定义为T2和所谓的低T2的患者中,也有部分疗效.Tezepelumab是防止TSLP-TSLPR相互作用的人抗TSLP抗体。一些临床试验正在评估Tezepelumab在各种炎症性疾病中的安全性和有效性。在这次审查中,我们将强调在理解TSLP的功能作用方面的最新进展,它参与Th2相关疾病,及其作为生物治疗目标的适用性。