上皮来源胸腺基质淋巴细胞生成素(TSLP)在过敏性疾病中的研究进展

Progress of epithelial-derived thymic stromal lymphopoietin (TSLP) in allergic diseases:An update

胸腺基质淋巴细胞生成素(TSLP)是影响过敏性疾病发生发展的重要因子。其单核苷酸多态性与过敏性疾病的易感性、病程和严重程度密切相关。过敏原暴露后,上皮细胞的多个信号途径介导TSLP表达,诱发免疫级联反应。TSLP通过抑制紧密连接、黏附连接和桥粒的表达,破坏脂质层,参与上皮物理屏障损伤;TSLP的两个异构体具有抗菌性可以增强皮肤及黏膜的防御能力,且在炎症早期TSLP可以上调紧密连接蛋白表达发挥屏障保护作用。在过敏性疾病中,TSLP通过其受体途径参与多种免疫细胞增殖、分化并释放促炎因子和趋化因子,介导免疫炎症。TSLP还通过诱导纤维细胞迁移与募集、促进上皮-间质转化等方式参与呼吸系统过敏的气道重塑过程。所以,TSLP阻断可能是治疗过敏性疾病的潜在靶点,TSLP靶向的生物制剂是今后过敏性疾病的治疗选择及研究方向。

Thymic stromal lymphopoietin(TSLP)is an important factor that affects the development of allergic diseases.Single nucleotide polymorphism of TSLP is closely related to the susceptibility,course and severity of allergic diseases.Following exposure to allergens,multiple signalling pathways in epithelial cells mediate TSLP expression and induce an immune cascade.TSLP affects epithelial physical barrier damage by inhibiting the expression of tight junctions,adhesion junctions and desmosomes and destroying the lipid layer.Two isomers of TSLP have antibacterial properties and can enhance the defence ability of the skin and mucosa.Moreover,TSLP plays a protective role by up-regulating the expression of tight junction proteins during early inflammation.In allergic diseases,TSLP participates in the proliferation and differentiation of various immune cells through the TSLP receptor pathway and releases pro-inflammatory and chemokine factors,thus mediating immune inflammation.Furthermore,TSLP is involved in airway remodelling in respiratory allergies by inducing fibrocyte migration and recruitment and promoting epithelial-mesenchymal transformation.Therefore,inhibition of TSLP may be a potential target for the treatment of allergic diseases.Research on biological agents targeted by TSLP is warranted for the treatment of allergic diseases in the future.