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Abstract：
Thymic stromal lymphopoietin (TSLP) was identified more than 20 years ago as a secreted factor of a mouse thymic stromal cell line; later, a human orthologue was also identified. The signaling pathway triggered by TSLP has been extensively studied, and upregulation of the cytokine itself is linked to the pathogenesis of numerous Th2-related diseases, including atopic dermatitis, asthma, allergic responses, as well as certain types of cancers. On the other hand, TSLP mediates several immune homeostatic functions in both the gut and the thymus. Thus, a paradox occurs; why is TSLP homeostatic in certain tissues and a hallmark of exacerbated Th2 responses in the aforementioned pathologies? We and others have recently shown that in humans a novel isoform exists; this is a shorter isoform of TSLP whose expression is constitutive and controlled by a separate promoter. Short TSLP isoform mediates the homeostatic functions, whereas the long isoform is expressed at low/undetectable level at steady state and upregulated during inflammation in several tissues. Here we review the most recent data concerning the differential expression of the 2 isoforms and provide a potential explanation to the paradox. TSLP is regarded as a promising target for treatment of relevant pathologies, with a number of clinical trials already underway. It is important to design new strategies aimed at leaving intact the homeostatic effects of the short isoform while targeting the inflammatory effects of the long isoform.
摘要：
胸腺基质淋巴细胞生成素（TSLP）在20多年前被确定为小鼠胸腺基质细胞系的分泌因子；后来，还确定了人类直系同源物。由TSLP触发的信号通路已被广泛研究,细胞因子本身的上调与许多Th2相关疾病的发病机理有关，包括特应性皮炎,哮喘,过敏反应,以及某些类型的癌症。另一方面,TSLP介导肠道和胸腺中的几种免疫稳态功能。因此，出现了一个悖论；为什么TSLP在某些组织中处于稳态，并且在上述病理中具有加剧的Th2反应的标志？我们和其他人最近表明，在人类中存在一种新的同种型；这是TSLP的较短同种型，其表达是组成型的并由单独的启动子控制。短TSLP同工型介导稳态功能，而长同工型在稳态下以低/不可检测的水平表达，并在炎症过程中在几种组织中上调。在这里，我们回顾了有关2种同工型差异表达的最新数据，并为该悖论提供了潜在的解释。TSLP被认为是治疗相关病理的有希望的目标，一些临床试验已经在进行中。重要的是设计旨在保持短同工型的稳态效应完整,同时靶向长同工型的炎症效应的新策略。
