Inflammation–fibrosis coupling in androgenetic alopecia: evidence and mechanistic hypotheses for progressive hair follicle miniaturization
- 1Institute of Regenerative Medicine, and Department of Dermatology, Affiliated Hospital of Jiangsu University, Jiangsu University , , ,
Abstract
Androgenetic alopecia (AGA) is primarily explained by genetic susceptibility and androgen-dependent signaling in dermal papilla cells. This mini-review examines whether low-grade, regionally heterogeneous perifollicular inflammation interacts with extracellular matrix remodeling as a complementary component of AGA pathobiology, without implying an autoimmune mechanism. Human AGA scalp studies report upper-follicular and perifollicular CD4+ lymphocytes, mast cells, immune-enriched transcriptional states, connective tissue sheath abnormalities, and fibrosis in subsets of patients. Patient-derived cells, ex vivo follicles, animal models, and cross-disease studies provide additional support for transforming growth factor-β, interleukin-6, prostaglandin D2, Wnt antagonism, oxidative stress, mitochondrial dysfunction, and cellular senescence. These signals could recruit or retain immune cells and shift dermal sheath cells or perifollicular fibroblasts toward matrix-producing and contractile states. Collagen accumulation, altered matrix turnover, stiffness, vascular restriction, and impaired epithelial–mesenchymal crosstalk may then reduce regenerative plasticity and stabilize miniaturization. Human evidence is strongest for androgen-dependent follicular stress and regional inflammatory or fibrotic changes. Specific immune-to-fibroblast circuits, mechanotransduction pathways, and their temporal sequence are supported mainly by experimental models or cross-disease evidence. Spatially resolved inflammation–fibrosis endotypes may help explain variation in treatment response and guide biomarker-enriched trials, but would not by themselves imply an autoimmune pathogenesis.
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BibTeX
@article{li2026inflammationfibrosis,
title = {{Inflammation–fibrosis coupling in androgenetic alopecia: evidence and mechanistic hypotheses for progressive hair follicle miniaturization}},
author = {Yi Li and Xiaoyue Wan and Yun Geng and Wenlong Zhu and Hui Xu and Yuyun Xiong and Yunwen Zheng and Yumei Li},
journal = {Frontiers in immunology},
year = {2026},
month = sep,
doi = {10.3389/fimmu.2026.1960477},
url = {https://europepmc.org/article/PMC/PMC13662793},
note = {CC BY},
}
RIS
TY - JOUR
TI - Inflammation–fibrosis coupling in androgenetic alopecia: evidence and mechanistic hypotheses for progressive hair follicle miniaturization
AU - Yi Li
AU - Xiaoyue Wan
AU - Yun Geng
AU - Wenlong Zhu
AU - Hui Xu
AU - Yuyun Xiong
AU - Yunwen Zheng
AU - Yumei Li
PY - 2026
DA - 2026/09/30
JO - Frontiers in immunology
DO - 10.3389/fimmu.2026.1960477
UR - https://europepmc.org/article/PMC/PMC13662793
AB - Androgenetic alopecia (AGA) is primarily explained by genetic susceptibility and androgen-dependent signaling in dermal papilla cells. This mini-review examines whether low-grade, regionally heterogeneous perifollicular inflammation interacts with extracellular matrix remodeling as a complementary component of AGA pathobiology, without implying an autoimmune mechanism. Human AGA scalp studies report upper-follicular and perifollicular CD4+ lymphocytes, mast cells, immune-enriched transcriptional states, connective tissue sheath abnormalities, and fibrosis in subsets of patients. Patient-derived cells, ex vivo follicles, animal models, and cross-disease studies provide additional support for transforming growth factor-β, interleukin-6, prostaglandin D2, Wnt antagonism, oxidative stress, mitochondrial dysfunction, and cellular senescence. These signals could recruit or retain immune cells and shift dermal sheath cells or perifollicular fibroblasts toward matrix-producing and contractile states. Collagen accumulation, altered matrix turnover, stiffness, vascular restriction, and impaired epithelial–mesenchymal crosstalk may then reduce regenerative plasticity and stabilize miniaturization. Human evidence is strongest for androgen-dependent follicular stress and regional inflammatory or fibrotic changes. Specific immune-to-fibroblast circuits, mechanotransduction pathways, and their temporal sequence are supported mainly by experimental models or cross-disease evidence. Spatially resolved inflammation–fibrosis endotypes may help explain variation in treatment response and guide biomarker-enriched trials, but would not by themselves imply an autoimmune pathogenesis.
SN - 1664-3224
ER -