Neuroepithelial signalling of tactile stimulus in the human hair follicle

Abstract

Touch relies upon the most intimate of our senses. It enables us to feel our surroundings, to feel pleasure or pain and to interact with our loved ones. The hair follicle (HF) is an important mediator of touch perception innervated by low-threshold mechanoreceptors (LTMRs), a diverse group of tactile sensory neurons forming lanceolate and circumferential endings around the follicle. In this thesis I used a combination of immunofluorescent and microscopy approaches, combined with electroanalytical methods to evaluate the role of the HF epithelium in touch perception. I found that terminal human HFs are innervated by 5 different types of these neurons in the outer root sheath (ORS) where the HF epithelium has its stem cell niche. HF epithelial cells are capable to respond to tactile-like stimulus by activation of mechanosensitive ion channel, once activated, ORS cells are able to send signalling molecules such as ATP, serotonin and histamine to surrounding LTMRs. Using pharmacology to block specific histamine and serotonin receptors, LTMRs diminishes their response, suggesting that ORS cells can activate neurons using these neurotransmitters after tactile-like stimulus. Comparing to skin keratinocytes, both cell types can release histamine but interestingly, only ORS cells release serotonin. These results suggest that the HF epithelium is a special niche in the way it responds to tactile-like stimuli. Overall, these results are the first stone to investigate the relationship between ORS cells and LTMRs in touch perception.