中山大学唐策课题组取得一项新突破。他们的最新研究揭示了Dectin-1促进肺真菌介导的肺纤维化。2025年6月9日出版的《免疫学》发表了这项成果。

在这项研究中，研究团队发现博莱霉素诱导的肺纤维化在Dectin-1缺陷小鼠中被抑制，这是通过与共生肺真菌Engyodontium相互作用介导的。Dectin-1主要在肺泡巨噬细胞（AMs）上表达，在人和小鼠中与纤维化严重程度相关。Dectin-1缺乏可降低精氨酸酶-1和TGF-β生成AMs及促纤维化因子的表达。在机制上，Dectin-1信号通路通过Raf1依赖途径促进静止AM分化为纤维化AM，绕过CARD9信号通路和单核巨噬细胞趋化募集。用层粘连蛋白或Raf1抑制剂靶向治疗Dectin-1可减轻小鼠的纤维化，降低人AM和成纤维细胞中的促纤维化因子。这些发现突出了Dectin-1-Raf1轴作为肺纤维化的关键调节因子和纤维化疾病的有希望的治疗靶点。

据了解，Dectin-1（Clec7a）是β-葡聚糖的C型凝集素受体，在宿主防御真菌感染中起关键作用，并与过敏反应有关，但其在肺纤维化中的作用尚不清楚。

附：英文原文

Title: Dectin-1 facilitates lung fungal-mediated pulmonary fibrosis

Author: Ding Qiu, Shuishen Zhang, Chanyan Huang, Xinying Wang, Jianping Deng, Haiyang Sun, Bingbing Feng, Ying Tan, Kaile Ji, Shaoting Xu, Xiaoqi Ye, Chao Cheng, Shigeru Kakuta, Yoshiyuki Adachi, Yoichiro Iwakura, Shuai Wang, Shaowei Dong, Ce Tang

Issue&Volume: 2025-06-09

Abstract: Dectin-1 (Clec7a), a C-type lectin receptor for β-glucans, is critical in host defense against fungal infections and has been implicated in allergic responses, yet its role in pulmonary fibrosis remains unclear. In this study, we reveal that bleomycin-induced pulmonary fibrosis was suppressed in Dectin-1-deficient mice, mediated by interactions with the commensal lung fungus Engyodontium. Dectin-1 was predominantly expressed on alveolar macrophages (AMs), correlating with fibrosis severity in both humans and mice. Dectin-1 deficiency reduced Arginase-1 and TGF-β-producing AMs and profibrotic factor expression. Mechanistically, Dectin-1 signaling promoted quiescent AM differentiation into profibrotic AMs via the Raf1-dependent pathway, bypassing CARD9 signaling and mono-macrophage chemotactic recruitment. Therapeutic targeting of Dectin-1 with laminarin or Raf1 inhibitors attenuated fibrosis in mice and reduced profibrotic factors in human AMs and fibroblasts. These findings highlight the Dectin-1-Raf1 axis as a key regulator of pulmonary fibrosis and a promising therapeutic target for fibrotic diseases.

DOI: 10.1016/j.immuni.2025.05.007

Source: https://www.cell.com/immunity/abstract/S1074-7613(25)00228-6