IL-6-Mediated Macrophage–Fibroblast Communication in Pathological Lung Remodeling
- 1Immunobiology and Biomedicine Division, Center for Genetics and Life Sciences, Sirius University of Science and Technology, 354340 Sochi, Russia
- 2Laboratory of Molecular Mechanisms of Immunity, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia
- 3Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia
Abstract
Fibrosis is a pathological form of tissue remodeling driven by excessive deposition of extracellular matrix (ECM). Unlike physiological tissue repair, fibrosis arises from persistent myofibroblast activation and unresolved inflammation. Chronic inflammation can both initiate fibrotic remodeling and be sustained by the resulting tissue alterations, supporting the view of fibrosis as an immune-mediated process. Fibrogenesis is fundamentally shaped by interactions between macrophages and fibroblasts. Polarized macrophages can modulate fibroblast activity and promote their differentiation into myofibroblasts. IL-6 is an important mediator of macrophage–fibroblast communication and has been implicated in fibrotic diseases affecting multiple organs. Notably, the effects of IL-6 are highly context-dependent. During acute injury, IL-6 can promote tissue repair by stimulating epithelial proliferation and angiogenesis, whereas persistent IL-6 signaling in chronic inflammation can become a major driver of fibrosis. IL-6 is also a prominent component of the senescence-associated secretory phenotype (SASP), providing a mechanistic link between fibrosis, cellular senescence, and inflammaging. In this review, we provide an integrated overview of the role of IL-6 in macrophage–fibroblast interactions during pulmonary fibrogenesis, with particular emphasis on its context-dependent functions at the interface between tissue repair and pathological tissue remodeling. We also discuss current therapeutic strategies aimed at targeting IL-6 signaling.
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BibTeX
@article{chicherina2026il6mediated,
title = {{IL-6-Mediated Macrophage–Fibroblast Communication in Pathological Lung Remodeling}},
author = {Nelya R. Chicherina and Ekaterina O. Gubernatorova and Olga A. Namakanova and Fedor A. Sysonov and Ekaterina A. Gorshkova and Marina S. Drutskaya},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = nov,
doi = {10.3390/ijms27219979},
url = {https://www.mdpi.com/1422-0067/27/21/9979},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - IL-6-Mediated Macrophage–Fibroblast Communication in Pathological Lung Remodeling
AU - Nelya R. Chicherina
AU - Ekaterina O. Gubernatorova
AU - Olga A. Namakanova
AU - Fedor A. Sysonov
AU - Ekaterina A. Gorshkova
AU - Marina S. Drutskaya
PY - 2026
DA - 2026/11/07
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219979
UR - https://www.mdpi.com/1422-0067/27/21/9979
AB - Fibrosis is a pathological form of tissue remodeling driven by excessive deposition of extracellular matrix (ECM). Unlike physiological tissue repair, fibrosis arises from persistent myofibroblast activation and unresolved inflammation. Chronic inflammation can both initiate fibrotic remodeling and be sustained by the resulting tissue alterations, supporting the view of fibrosis as an immune-mediated process. Fibrogenesis is fundamentally shaped by interactions between macrophages and fibroblasts. Polarized macrophages can modulate fibroblast activity and promote their differentiation into myofibroblasts. IL-6 is an important mediator of macrophage–fibroblast communication and has been implicated in fibrotic diseases affecting multiple organs. Notably, the effects of IL-6 are highly context-dependent. During acute injury, IL-6 can promote tissue repair by stimulating epithelial proliferation and angiogenesis, whereas persistent IL-6 signaling in chronic inflammation can become a major driver of fibrosis. IL-6 is also a prominent component of the senescence-associated secretory phenotype (SASP), providing a mechanistic link between fibrosis, cellular senescence, and inflammaging. In this review, we provide an integrated overview of the role of IL-6 in macrophage–fibroblast interactions during pulmonary fibrogenesis, with particular emphasis on its context-dependent functions at the interface between tissue repair and pathological tissue remodeling. We also discuss current therapeutic strategies aimed at targeting IL-6 signaling.
SN - 1422-0067
ER -