Abstract
The etiology of hair loss remains enigmatic, and current remedies remain inadequate. Transcriptome analysis of aging hair follicles uncovered changes in immune pathways, including Toll-like receptors (TLRs). Our findings demonstrate that the maintenance of hair follicle homeostasis and the regeneration capacity after damage depends on TLR2 in hair follicle stem cells (HFSCs). In healthy hair follicles, TLR2 is expressed in a cycle-dependent manner and governs HFSCs activation by countering inhibitory BMP signaling. Hair follicles in aging and obesity exhibit a decrease in both TLR2 and its endogenous ligand carboxyethylpyrrole (CEP), a metabolite of polyunsaturated fatty acids. Administration of CEP stimulates hair regeneration through a TLR2-dependent mechanism. These results establish a novel connection between TLR2-mediated innate immunity and HFSC activation, which is pivotal to hair follicle health and the prevention of hair loss and provide new avenues for therapeutic intervention.
Summary Hair follicle stem cells TLR2 is required for hair homeostasis and regeneration. While TLR2 stimulation by endogenous ligand promotes hair growth, reduction in TLR2 and its ligand in aging and obesity may diminish hair growth.
Competing Interest Statement
Dr. Byzova has a relevant patent 9,981,018 Compositions and Methods for Modulating Toll-Like Receptor 2 Activation
Footnotes
The original figure 4 was missing panel D, therefore, it was added to the revised version.
List of abbreviations
- TLR
- toll-like receptor
- HFs
- hair follicles
- HFSCs
- hair follicle stem cells
- CEP
- carboxyethylpyrrole
- MPO
- myeloperoxidase
- PUFA
- polyunsaturated fatty acid
- sHG
- secondary hair germ
- DP
- dermal papilla
- ORS
- outer root sheath
- IRS
- inner root sheath
- MPPs
- multipotent progenitors
- NHEK
- human epidermal keratinocytes
- HFDPC
- hair follicle dermal papilla cells
