Adhikary Partho Protim, Tan Zheng, Page Brent D G, Hedtrich Sarah
Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver Campus, Vancouver, BC V6T 1Z3, Canada.
Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver Campus, Vancouver, BC V6T 1Z3, Canada; Department of Oncology and Pathology, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden.
Pharmacol Ther. 2021 Jan;217:107648. doi: 10.1016/j.pharmthera.2020.107648. Epub 2020 Aug 3.
Atopic diseases refer to common allergic inflammatory diseases such as atopic dermatitis (AD), allergic rhinitis (AR), and allergic asthma (AA). AD often develops in early childhood and may herald the onset of other allergic disorders such as food allergy (FA), AR, and AA. This progression of the disease is also known as the atopic march, and it goes hand in hand with a significantly impaired quality of life as well as a significant economic burden. Atopic diseases usually are considered as T helper type 2 (Th2) cell-mediated inflammatory diseases. Thymic stromal lymphopoietin (TSLP), an epithelium-derived pro-inflammatory cytokine, activates distinct immune and non-immune cells. It has been shown to be a master regulator of type 2 immune responses and atopic diseases. In experimental settings, the inhibition or knockout of TSLP signaling has shown great therapeutic potential. This, in conjunction with the increasing knowledge about the central role of TSLP in the pathogenesis of atopic diseases, has sparked an interest in TSLP as a druggable target. In this review, we will discuss the autocrine and paracrine effects of TSLP, how it regulates the tissue microenvironment and drives atopic diseases, which provide the rationale for the increasing interest in TSLP as a druggable target.
特应性疾病是指常见的过敏性炎症性疾病,如特应性皮炎(AD)、过敏性鼻炎(AR)和过敏性哮喘(AA)。AD通常在儿童早期发病,可能预示着其他过敏性疾病的发生,如食物过敏(FA)、AR和AA。这种疾病的进展也被称为特应性进程,它与生活质量显著受损以及巨大的经济负担密切相关。特应性疾病通常被认为是2型辅助性T(Th2)细胞介导的炎症性疾病。胸腺基质淋巴细胞生成素(TSLP)是一种上皮来源的促炎细胞因子,可激活不同的免疫细胞和非免疫细胞。它已被证明是2型免疫反应和特应性疾病的主要调节因子。在实验环境中,抑制或敲除TSLP信号已显示出巨大的治疗潜力。这与对TSLP在特应性疾病发病机制中的核心作用的认识不断增加相结合,引发了人们对将TSLP作为可成药靶点的兴趣。在这篇综述中,我们将讨论TSLP的自分泌和旁分泌作用,它如何调节组织微环境并驱动特应性疾病,这为人们对将TSLP作为可成药靶点的兴趣日益增加提供了理论依据。