Stress-induced sympathetic hyperactivation drives hair follicle necrosis to trigger autoimmunity
Year: 2025
Type: article
Abstract: Stress has profound effects on health, yet how it damages tissues remains poorly understood. Here, we show that acute stress triggers rapid hair loss and initiates autoimmunity. Under stress, hyperactivated sympathetic nerves release excessive norepinephrine, causing necrosis in rapidly dividing hair follicle transit-amplifying cells (HF-TACs) while sparing most hair follicle stem cells (HFSCs). This differential sensitivity stems from differences in cell death pathways, metabolic strategies, and calcium homeostasis, which render HF-TACs more susceptible to norepinephrine-induced calcium surges. HF-TAC necrosis releases cellular debris that triggers macrophage-mediated clearance and dendritic cell activation, ultimately leading to the activation and amplification of autoreactive T cells that can attack the hair follicle under inflammatory insults. Our findings reveal mechanistically how stress causes immediate tissue damage in highly proliferative HF-TACs via sympathetic nerve-induced necrosis, which in turn fuels the activation of autoreactive T cells capable of mounting future attacks against the same tissue.
Source: Cell
Authors: Emily Scott-Solomon, Shlomi Brielle, Alexander O. Mann, Mark J. Khoury, Jingyu Peng, Liana Tellez, Mackenzie Harrigan, Myrto Ziogas, H. Amalia Pasolli, Monica Cassandras, Adam J. Getzler, Rebecca Freeman, Bing Zhang, Yulia Shwartz, Judith Agudo, Ruth A. Franklin, Ya-Chieh Hsu
Language: English
Topic: Hair Growth and Disorders
Subfield: Urology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $11,400
Funders: National Science Foundation, Richard and Susan Smith Family Foundation, Glenn Foundation for Medical Research, New York Stem Cell Foundation, Helen Hay Whitney Foundation, Harvard Medical School, Charles A. King Trust, LEO Fondet, National Institutes of Health, Harvard Stem Cell Institute, National Cancer Institute, National Institute of Arthritis and Musculoskeletal and Skin Diseases
Awards: G1315471222, Aging and Rejuvenation of Skin Stem Cells, G3149882656, G4816627311, G5529748454, G7355440228, Defining Sexual Dimorphism in the Skin, Rapid functional genetics to study stem cell-niche interactions in the skin, Engineering dendritic cells to target islet antigen to pro-tolerogenic subsets for prevention and treatment of Type 1 Diabetes, Interrogating the role of IFNgamma in promoting metastasis and immune evasion of triple negative breast cancer
OpenAlex ID: W4416702280