The hair follicle as a neuro-immuno-endocrine organ: Implications in hair disorders and regenerative therapies

Background: The hair follicle (HF) is no longer viewed as a passive mini-organ of hair production. It functions as a dynamic neuro-immuno-endocrine interface that actively communicates with its surrounding microenvironment. Understanding the HF's multifaceted signaling axes is essential for decoding hair pathology and innovating regenerative therapies. Objectives: This review explores the integrative physiology of the HF as a neuro-immuno-endocrine organ, its relevance in major hair disorders, and emerging regenerative interventions that target its complex signaling networks. Methods: A systematic literature search was performed using PubMed, Scopus, and Embase databases up to July 2025, following PRISMA guidelines. Studies focusing on neurogenic, immunologic, endocrine, and regenerative aspects of the HF were included. Results: The HF displays intrinsic sensory, immune, and endocrine signaling pathways, with key implications in alopecia areata, androgenetic alopecia, and cicatricial alopecias. Neurogenic inflammation, immune privilege collapse, and hormonal dysregulation disrupt hair cycling and contribute to pathology. Recent therapeutic advances—including PRP, stem cell-based approaches, and neuromodulatory strategies—leverage these pathways for follicular regeneration. Conclusion: Recognizing the HF as a neuro-immuno-endocrine organ unveils novel therapeutic targets in hair disorders. Future translational studies should focus on restoring HF homeostasis via its regulatory axes to optimize clinical outcomes in regenerative dermatology.