2. Academic Validation
  3. Macrophage-derived IL-1β directs fibroblast progenitor cell fate via metabolic reprogramming in wound healing

Macrophage-derived IL-1β directs fibroblast progenitor cell fate via metabolic reprogramming in wound healing

  • Commun Biol. 2025 Aug 27;8(1):1291. doi: 10.1038/s42003-025-08754-w.
Huanyu Luo # 1 2,  Xiaoyi Yu # 1 2,  Tianmeng Sun 1 2,  Zewen Sun 1 2,  Tianyuan Zhao 1 2,  Chen Li 3,  Ana Angelova Volponi 4,  Fabian Flores-Borja 5,  Hongchen Sun 6,  Zhengwen An 7 8
Affiliations

Affiliations

  • 1 Department of Oral Biology, School and Hospital of Stomatology, Jilin University, Changchun, China.
  • 2 Key Laboratory of Tooth Development and Bone Remodeling of Jilin Province, School and Hospital of Stomatology, Jilin University, Changchun, China.
  • 3 Department of Oral Mucosa Disease & Oral Emergency, School and Hospital of Stomatology, Jilin University, Changchun, China.
  • 4 Centre for Craniofacial and Regenerative Biology, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London, UK.
  • 5 Centre for Oral Immunobiology and Regenerative Medicine, Barts & The London School of Medicine and Dentistry, Queen Mary University of London, Blizard Institute, London, UK.
  • 6 Department of Oral Pathology, School and Hospital of Stomatology, Jilin University, Changchun, China. hcsun@jlu.edu.cn.
  • 7 Department of Oral Biology, School and Hospital of Stomatology, Jilin University, Changchun, China. wenny_an@jlu.edu.cn.
  • 8 Key Laboratory of Tooth Development and Bone Remodeling of Jilin Province, School and Hospital of Stomatology, Jilin University, Changchun, China. wenny_an@jlu.edu.cn.
  • # Contributed equally.
PMID: 40866544 DOI: 10.1038/s42003-025-08754-w
Abstract

The oral mucosa exhibits unique regenerative properties and distinct wound healing dynamics compared to facial skin, providing a valuable model for studying tissue-specific repair mechanisms. Using a rigorously controlled mouse model combined with single-cell transcriptomics, we identified a novel mechanism underlying this tissue-specific difference. Our study revealed a population of fibroblast progenitors in the oral buccal mucosa that rapidly activate and differentiate into mature fibroblasts, contributing to effective wound resolution. Mechanistically, IL-1β derived from tissue-resident macrophages activates NFκB signals in these progenitors, inducing a metabolic shift from glycolysis to Oxidative Phosphorylation in a proteasome-dependent manner. This metabolic reprogramming supports stem cell differentiation and contributes to the unique regenerative pattern of the oral buccal mucosa. Our findings highlight the specialized healing mechanisms of the oral tissue and suggest that modulating Proteasome activation and the IL-1β/NFκB axis may offer new therapeutic avenues for enhancing wound repair in tissue requiring extensive connective remodeling, such as skin or gingiva.

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