Cai Chen, Guan Lanxi, Wang Chenhao, Hu Runjie, Ou Lingling, Jiang Qianzhou
Department of Endodontics, School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction & Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University, Guangzhou, China.
Department of Periodontics, School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction & Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University, Guangzhou, China.
Front Immunol. 2025 May 23;16:1588667. doi: 10.3389/fimmu.2025.1588667. eCollection 2025.
Neutrophil-fibroblast crosstalk drives inflammatory pathology across organ systems through both shared and tissue-specific mechanisms. This review synthesizes evidence from skin, lung, gut, cardiovascular, joint, sinus, and oral diseases, revealing conserved molecular pathways where fibroblasts secrete chemokines (CXCL1/8/12) to recruit neutrophils, which, in turn, release neutrophil extracellular traps (NETs), elastase, and cytokines to modulate fibroblast function. Additionally, we identify critical tissue-specific differences, including the predominance of IL-36 signaling in COPD, IL-17-carrying NETs in systemic lupus erythematosus (SLE) and pulmonary fibrosis, and specialized fibroblast subpopulations, such as IDO1+ cells in CRSwNP and TNFRSF21+ cells in periodontitis. Translational insights highlight the therapeutic potential of targeting IL-17, NETs, and fibroblast subpopulations, though tissue-specific risks necessitate precision strategies. Future therapeutic efforts should focus on developing precision-targeted interventions that address organ-specific mechanisms to overcome treatment resistance in inflammatory disorders.
中性粒细胞与成纤维细胞的相互作用通过共同机制和组织特异性机制驱动跨器官系统的炎症病理过程。本综述综合了来自皮肤、肺、肠道、心血管、关节、鼻窦和口腔疾病的证据，揭示了保守的分子途径，即成纤维细胞分泌趋化因子（CXCL1/8/12）以招募中性粒细胞，而中性粒细胞反过来释放中性粒细胞胞外诱捕网（NETs）、弹性蛋白酶和细胞因子来调节成纤维细胞功能。此外，我们还确定了关键的组织特异性差异，包括慢性阻塞性肺疾病（COPD）中IL-36信号的主导地位、系统性红斑狼疮（SLE）和肺纤维化中携带IL-17的NETs，以及特殊的成纤维细胞亚群，如慢性鼻-鼻窦炎伴鼻息肉（CRSwNP）中的吲哚胺2,3-双加氧酶1（IDO1）阳性细胞和牙周炎中的肿瘤坏死因子受体超家族成员21（TNFRSF21）阳性细胞。转化医学见解突出了靶向IL-17、NETs和成纤维细胞亚群的治疗潜力，尽管组织特异性风险需要精准策略。未来的治疗努力应集中于开发精准靶向干预措施，以解决器官特异性机制，克服炎症性疾病中的治疗抵抗。
