Stress-Induced Sympathetic Hyperactivation Drives Hair Follicle Necrosis to Trigger Autoimmunity

This study demonstrates that acute stress can lead to rapid hair loss and trigger autoimmunity by causing necrosis in hair follicle transit-amplifying cells (HF-TACs) through hyperactivated sympathetic nerves releasing excessive norepinephrine. While most hair follicle stem cells (HFSCs) are spared, HF-TACs are more vulnerable due to differences in cell death pathways, metabolic strategies, and calcium homeostasis. The necrosis of HF-TACs results in the release of cellular debris, which activates macrophages and dendritic cells, leading to the activation of autoreactive T cells. These T cells can then attack the hair follicle, especially under inflammatory conditions, revealing a mechanism by which stress-induced sympathetic hyperactivation causes tissue damage and fuels autoimmunity.