Inflammation–fibrosis coupling in androgenetic alopecia: evidence and mechanistic hypotheses for progressive hair follicle miniaturization

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.