Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan. t−
Allergol Int. 2012 Mar;61(1):3-17. doi: 10.2332/allergolint.11-RAI-0395. Epub 2012 Jan 25.
Thymic stromal lymphopoietin (TSLP) is an IL-7-like cytokine initially identified in the culture supernatant of a thymic stromal cell line. Highly expressed in the epidermis in skin lesions of atopic dermatitis patients, TSLP was subsequently found to be a critical factor linking responses at interfaces between the body and environment (skin, airway, gut, ocular tissues, and so on) to Th2 responses. Recent studies have revealed that various cell types other than epithelial cells and epidermal keratinocytes (such as mast cells, airway smooth muscle cells, fibroblasts, dendritic cells, trophoblasts, and cancer or cancer-associated cells) also express TSLP. Environmental factors such as Toll-like receptor ligands, a Nod2 ligand, viruses, microbes, allergen sources, helminths, diesel exhaust, cigarette smoke, and chemicals trigger TSLP production. Proinflammatory cytokines, Th2-related cytokines, and IgE also induce or enhance TSLP production, indicating cycles of amplification. Skin barrier injury, increased epidermal endogenous protease activity, and less epidermal Notch signaling, all of which have been reported in atopic dermatitis, and keratinocyte-specific loss of retinoid X receptors and treatment of skin with agonists for vitamin D receptor in mice induce TSLP production, Th2 response, or atopic dermatitis-like inflammation. The transcription factors NF-κB and AP-1, nuclear receptors, single nucleotide polymorphisms, microRNAs, and the peptidyl-proryl isomerase Pin1 regulate TSLP mRNA expression transcriptionally or posttranscriptionally. This review focuses on events upstream of TSLP production, which is critical in allergic diseases and important in other TSLP-related disorders i.e. production sites, cellular sources, environmental and endogenous triggers and regulatory factors, and regulatory mechanisms of gene expression.
胸腺基质淋巴细胞生成素 (TSLP) 是一种最初在胸腺基质细胞系的培养上清液中鉴定的 IL-7 样细胞因子。在特应性皮炎患者的皮肤损伤表皮中高度表达，随后发现 TSLP 是将身体和环境（皮肤、气道、肠道、眼部组织等）之间的反应与 Th2 反应联系起来的关键因素。最近的研究表明，除上皮细胞和表皮角质形成细胞（如肥大细胞、气道平滑肌细胞、成纤维细胞、树突状细胞、滋养细胞和癌症或癌症相关细胞）以外，各种细胞类型也表达 TSLP。环境因素，如 Toll 样受体配体、Nod2 配体、病毒、微生物、过敏原来源、寄生虫、柴油废气、香烟烟雾和化学物质，可触发 TSLP 产生。促炎细胞因子、Th2 相关细胞因子和 IgE 也可诱导或增强 TSLP 产生，表明存在放大循环。特应性皮炎患者中已报道皮肤屏障损伤、表皮内源性蛋白酶活性增加和表皮 Notch 信号传导减少，角蛋白细胞特异性缺失视黄醇 X 受体和用维生素 D 受体激动剂处理皮肤可诱导 TSLP 产生、Th2 反应或特应性皮炎样炎症。转录因子 NF-κB 和 AP-1、核受体、单核苷酸多态性、microRNAs 和肽脯氨酰顺反异构酶 Pin1 转录或转录后调节 TSLP mRNA 表达。本综述重点介绍 TSLP 产生的上游事件，这在过敏疾病中至关重要，并且在其他与 TSLP 相关的疾病中也很重要，即产生部位、细胞来源、环境和内源性触发因素和调节因子以及基因表达的调节机制。
