AUTHOR=Cai Chen , Guan Lanxi , Wang Chenhao , Hu Runjie , Ou Lingling , Jiang Qianzhou 

TITLE=The role of fibroblast-neutrophil crosstalk in the pathogenesis of inflammatory diseases: a multi-tissue perspective

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1588667

DOI=10.3389/fimmu.2025.1588667

ISSN=1664-3224

ABSTRACT=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.