REVIEW article
Front. Immunol.
Sec. Inflammation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1609509
This article is part of the Research TopicUnraveling the Molecular Web of Inflammation and Fibrosis: Pathways, Immune Interactions, Epigenetics, and Therapeutic FrontiersView all 7 articles
Revisiting Pulmonary Fibrosis: Inflammatory Dynamics of the Lipofibroblast-to-Inflammatory Lipofibroblast-to-Activated Myofibroblast Reversible Switch
Provisionally accepted
Georgios-Dimitrios Panagiotidis1
Esmeralda Vásquez Pacheco2
Xuran Chu3
Werner Seeger1
Elie El Agha1
Saverio Bellusci2
Arun Lingampally1*- 1Institute for Lung Health, University of Giessen, Giessen, Germany
- 2Cardio Pulmonary Institute (CPI), Giessen, Germany
- 3School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
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Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease characterized by excessive extracellular matrix (ECM) deposition and irreversible lung damage. A key driver of disease progression is the phenotypic shift of lipofibroblasts (LIFs) into activated myofibroblasts (aMYFs), triggered by sustained epithelial injury, caused by inflammation, oxidative stress, viral infections (e.g., influenza, SARS-CoV-2), and metabolic dysfunction. Emerging evidence demonstrates that this transition is reversible, with pharmacological agents that promote aMYF-to-LIF reprogramming contributing to fibrosis resolution. The identification of inflammatory lipofibroblasts (iLIFs) highlights the importance of inflammation in fibrosis progression. Inflammation, mediated by IL-1β, IL-17A, and TGF-β, sustain aMYF activation, while immune cells shape fibrosis formation. This review combines current insights on the cellular and molecular pathways controlling fibroblast differentiation, highlighting key metabolic, immunologic, and oxidative stress-modulating targets for therapeutic intervention. Understanding and manipulating the LIF-iLIF-aMYF axis offers a promising strategy for reversing fibrosis and restoring pulmonary homeostasis in IPF.
Keywords: Idiopathic Pulmonary Fibrosis, lipofibroblast, inflammatory lipofibroblast, activated myofibroblast, TGF-β, IL-17A, Inflammation, Virus infection
Received: 10 Apr 2025; Accepted: 26 May 2025.
Copyright: © 2025 Panagiotidis, Vásquez Pacheco, Chu, Seeger, El Agha, Bellusci and Lingampally. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Arun Lingampally, Institute for Lung Health, University of Giessen, Giessen, Germany
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