Immune cell fibrotic plasticity: mesenchymal-like reprogramming of macrophages, neutrophils and T cells
- 1Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University , ,
Abstract
Fibrosis has traditionally been viewed as a fibroblast- and myofibroblast-centred process, in which immune cells regulate matrix deposition primarily through inflammatory mediators and paracrine signalling. However, advances in single-cell profiling, spatial analyses and lineage-resolved approaches are beginning to challenge this rigid division of cellular labour. Emerging evidence indicates that, in persistently injured and maladaptively repairing tissues, selected immune cell populations can acquire matrix producing, cytoskeletal remodelling and mesenchymal-like functions, thereby contributing more directly to structural tissue remodelling. In this Review, we introduce the concept of immune cell fibrotic plasticity and critically assess the evidence, regulatory mechanisms and pathological significance of fibrotic effector states in macrophages, neutrophils and T cells. Macrophage reprogramming towards myofibroblast-like states appears to be shaped by convergent TGF-β/SMAD signalling, metabolic adaptation and epigenetic regulation. Neutrophils can synthesize, transport and organize extracellular matrix, conferring temporally distinct functions in tissue stabilization and pathological scarring. Evidence for mesenchymal-like reprogramming of T cells remains limited, but raises the possibility that adaptive immune cells can also acquire structural effector functions. Importantly, co-expression of immune and mesenchymal markers does not, by itself, establish stable lineage conversion. These phenomena are more appropriately understood as microenvironmentally induced, context-dependent functional states rather than universal or complete transdifferentiation. Defining the origins, reversibility and quantitative contribution of these states will determine whether immune-cell fibrotic plasticity can be exploited for disease stratification and the development of more selective antifibrotic therapies.
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BibTeX
@article{long2026immune,
title = {{Immune cell fibrotic plasticity: mesenchymal-like reprogramming of macrophages, neutrophils and T cells}},
author = {Xiaodan Long and Shaoxiang Yuan and Ziyi Luo and Yuezhong Chen and Shune Xiao and Chengliang Deng and Junzhe Chen},
journal = {Frontiers in immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1904807},
url = {https://europepmc.org/article/PMC/PMC13673658},
note = {CC BY},
}
RIS
TY - JOUR
TI - Immune cell fibrotic plasticity: mesenchymal-like reprogramming of macrophages, neutrophils and T cells
AU - Xiaodan Long
AU - Shaoxiang Yuan
AU - Ziyi Luo
AU - Yuezhong Chen
AU - Shune Xiao
AU - Chengliang Deng
AU - Junzhe Chen
PY - 2026
DA - 2026/10/02
JO - Frontiers in immunology
DO - 10.3389/fimmu.2026.1904807
UR - https://europepmc.org/article/PMC/PMC13673658
AB - Fibrosis has traditionally been viewed as a fibroblast- and myofibroblast-centred process, in which immune cells regulate matrix deposition primarily through inflammatory mediators and paracrine signalling. However, advances in single-cell profiling, spatial analyses and lineage-resolved approaches are beginning to challenge this rigid division of cellular labour. Emerging evidence indicates that, in persistently injured and maladaptively repairing tissues, selected immune cell populations can acquire matrix producing, cytoskeletal remodelling and mesenchymal-like functions, thereby contributing more directly to structural tissue remodelling. In this Review, we introduce the concept of immune cell fibrotic plasticity and critically assess the evidence, regulatory mechanisms and pathological significance of fibrotic effector states in macrophages, neutrophils and T cells. Macrophage reprogramming towards myofibroblast-like states appears to be shaped by convergent TGF-β/SMAD signalling, metabolic adaptation and epigenetic regulation. Neutrophils can synthesize, transport and organize extracellular matrix, conferring temporally distinct functions in tissue stabilization and pathological scarring. Evidence for mesenchymal-like reprogramming of T cells remains limited, but raises the possibility that adaptive immune cells can also acquire structural effector functions. Importantly, co-expression of immune and mesenchymal markers does not, by itself, establish stable lineage conversion. These phenomena are more appropriately understood as microenvironmentally induced, context-dependent functional states rather than universal or complete transdifferentiation. Defining the origins, reversibility and quantitative contribution of these states will determine whether immune-cell fibrotic plasticity can be exploited for disease stratification and the development of more selective antifibrotic therapies.
SN - 1664-3224
ER -