Lichen Planopilaris and Frontal Fibrosing Alopecia as Model Epithelial Stem Cell Diseases

The document examines Lichen Planopilaris (LPP) and Frontal Fibrosing Alopecia (FFA) as diseases that can provide insights into the pathology of epithelial stem cells (eSCs) in the hair follicle. It identifies interferon (IFN)-γ and peroxisome proliferator-activated receptor (PPAR)-γ-mediated signaling as key factors in the collapse of immune privilege (IP) and the process of epithelial-mesenchymal transition (EMT) in these stem cells, suggesting these pathways as potential therapeutic targets. The paper proposes that LPP and FFA share a common pathogenesis involving the depletion of eSCs and EMT, leading to permanent hair loss. It also notes an increase in FFA cases and suggests environmental and epigenetic factors may influence the disease. Potential treatments like PPAR-γ agonists and IP-restorative treatments are discussed, with the PPAR-γ agonist pioglitazone showing up to a 50% response rate. The document also explores various factors that may contribute to the development of FFA, including disrupted cholesterol biosynthesis, sex steroids, genetics, and oxidative stress. The paper emphasizes the importance of these conditions for understanding eSC function and dysfunction, despite the challenge of studying human eSC niches in extracutaneous tissues.