Department of Surgical Intensive Care Unit, Beijing An Zhen Hospital, Capital Medical University, Beijing, China.
Department of Pulmonary and Critical Care Medicine, Center for Respiratory Diseases, China-Japan Friendship Hospital, National Clinical Research Center for Respiratory Diseases, Beijing, China.
Clin Respir J. 2022 Nov;16(11):696-707. doi: 10.1111/crj.13541. Epub 2022 Sep 9.
Interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP) are the important drivers for excessive type-2 immunity. It has been well elucidated that IL-25/IL-33/TSLP plays an important role in allergic airway inflammation and remodeling, whereas their roles in idiopathic pulmonary fibrosis (IPF) still remained largely unclear. Herein, the aim of the review is to discuss the potential role and mechanism of IL-25/IL-33/TSLP on IPF by literature analysis and summary.
We have done a literature search using the following terms: ("idiopathic pulmonary fibrosis" OR "IPF" OR "lung fibrosis") and (TSLP or "thymic stromal lymphopoietin" or IL-25 OR IL-17E OR IL-33) from the database of PubMed published in English up to July 2018.
We have totally found 58 articles by using the retrieval terms mentioned above. By careful title and abstract reading, 10 original research articles of high quality were enrolled for the full text reading and analysis. Two additional relevant studies were also included during the course of literature readings.
IL-25/IL-33/TSLP and their corresponding receptors, that is, IL-17BR/ST2L/TSLPR, are shown to be up-regulated both in IPF patients and bleomycin (BLM)-induced lung fibrosis mice model. IL-25 may promote lung fibrosis by activating IL-17BR+fibroblast and IL-17BR+ILC2 (type 2 innate lymphoid cell). Full length (fl)-IL-33, as a transcription factor mainly in the cell nucleus, mediated non-atopic lung inflammation and fibrosis by modulating expressions of several pro-fibrotic mediators, including transforming growth factor (TGF)-b1. By contrast, mature (m)-IL-33 potentiates lung fibrosis by recruiting ST2L+M2 macrophages and ST2L+ILC2 to enlarge type 2 immunity. TSLP was shown to directly promote CCL2 expression in primary human lung fibroblasts (pHLFs).
IL-25/IL-33/TSLP contributes to non-allergic lung fibrosis by mediating persistent abnormal epithelial-mesenchymal crosstalk. IL-25/IL-33/TSLP may serve the promising novel target for the treatment of IPF.
白细胞介素（IL）-25、IL-33 和胸腺基质淋巴细胞生成素（TSLP）是过度 2 型免疫的重要驱动因素。已经充分阐明，IL-25/IL-33/TSLP 在过敏性气道炎症和重塑中发挥重要作用，而其在特发性肺纤维化（IPF）中的作用仍不清楚。在此，通过文献分析和综述，讨论了 IL-25/IL-33/TSLP 在 IPF 中的潜在作用和机制。
我们使用以下术语在 PubMed 数据库中进行了文献检索：（“特发性肺纤维化”或“IPF”或“肺纤维化”）和（TSLP 或“胸腺基质淋巴细胞生成素”或 IL-25 或 IL-17E 或 IL-33），检索时间截至 2018 年 7 月。
使用上述检索词共检索到 58 篇文章，通过仔细阅读标题和摘要，共纳入 10 篇高质量的原始研究文章进行全文阅读和分析。在文献阅读过程中，还纳入了另外 2 项相关研究。
IL-25/IL-33/TSLP 及其相应受体，即 IL-17BR/ST2L/TSLPR，在 IPF 患者和博来霉素（BLM）诱导的肺纤维化小鼠模型中均呈上调表达。IL-25 可能通过激活 IL-17BR+成纤维细胞和 IL-17BR+ILC2（2 型固有淋巴细胞）来促进肺纤维化。全长（fl）-IL-33 作为主要在细胞核中的转录因子，通过调节几种促纤维化介质的表达，包括转化生长因子（TGF）-b1，介导非变应性肺炎症和纤维化。相比之下，成熟（m）-IL-33 通过募集 ST2L+M2 巨噬细胞和 ST2L+ILC2 来扩大 2 型免疫，从而增强肺纤维化。TSLP 被证明可直接促进原代人肺成纤维细胞（pHLFs）中 CCL2 的表达。
IL-25/IL-33/TSLP 通过介导持续的异常上皮-间充质细胞相互作用，促进非过敏性肺纤维化。IL-25/IL-33/TSLP 可能成为治疗 IPF 的有前途的新型靶点。
