Asthma is a chronic respiratory disease characterized by airway inflammation and remodeling as well as hyper-responsiveness. Thymic stromal lymphopoietin (TSLP), which is a crucial inflammatory cytokine in immune homeostasis, consists of two isoforms, the long isoform lfTSLP and short isoform sfTSLP. The lfTSLP promotes inflammation and plays a pivotal role in asthma pathogenesis, while sfTSLP had been reported to have anti-asthma effects. Experiments have shown that lfTSLP could induce autophagy in hepatocytes. It is unknown whether lfTSLP or sfTSLP could influence autophagy and affect the progression of asthma. Using house dust mite (HDM)-stimulated airway smooth muscle cells as an in vitro model and HDM-induced asthma mice as in vivo model, we found that lfTSLP could induce autophagy and remodeling, while sfTSLP has the reverse effect. Strikingly, sfTSLP treatment in vivo reversed HDM-mediated activation of inflammation and airway remodeling, partly determined by autophagy change. These findings may help us understand the function of TSLP isoforms in the pathogenesis of asthma, and they support the use of drugs targeting sfTSLP and TSLP for asthma treatment.

哮喘是一种慢性呼吸道疾病，其特征是气道炎症和重塑以及高反应性。胸腺基质淋巴细胞生成素 (TSLP) 是免疫稳态中至关重要的炎症细胞因子，由两种亚型组成：长亚型 lfTSLP 和短亚型 sfTSLP。 lfTSLP 促进炎症并在哮喘发病机制中发挥关键作用，而 sfTSLP 据报道具有抗哮喘作用。实验表明lfTSLP可以诱导肝细胞自噬。目前尚不清楚 lfTSLP 或 sfTSLP 是否会影响自噬并影响哮喘的进展。使用屋尘螨（HDM）刺激的气道平滑肌细胞作为体外模型和HDM诱导的哮喘小鼠作为体内模型，我们发现lfTSLP可以诱导自噬和重塑，而sfTSLP具有相反的作用。引人注目的是，sfTSLP体内治疗逆转了 HDM 介导的炎症和气道重塑的激活，部分是由自噬变化决定的。这些发现可能有助于我们了解 TSLP 亚型在哮喘发病机制中的功能，并支持使用针对 sfTSLP 和 TSLP 的药物治疗哮喘。