Peripheral nerve fibres form multifacet interactions with keratinocytes in a novel complete human 2D culture model

Recent studies have demonstrated that keratinocytes closely participate in sensory transduction, and therefore, intra-epidermal free nerve endings are not exclusive transducers of pain. This discovery implies the existence of close afferent communication from keratinocytes to sensory neurons. Although reciprocal interactions between keratinocytes and intra-epidermal free nerve endings via soluble mediators are well established, little attention has been paid to physical contacts between keratinocytes and intra-epidermal free nerve endings. This review proposes to consider the ultrastructural and functional knowledge of these contacts, in both human skin biopsies and keratinocyte-sensory neuron cocultures to speculate on the possible existence of synaptic contacts. K E Y W O R D Scontact, keratinocyte, sensory neuron, skin, synapse

Section: Characterization Of Physical Contacts Between Keratinocytes supporting

confidence: 74%

What about physical contacts between epidermal keratinocytes and sensory neurons?

Talagas

Lebonvallet

Leschiera

et al. 2017

“…Studies employing transgenic mice have shown that solely stimulating epidermal keratinocytes are sufficient to induce nociceptive behaviour 6,7 . Additionally, keratinocytes have been shown to transmit sensory stimuli to neighbouring cells by releasing ATP or directly through cell‐cell contacts 8–14 . However, knowledge regarding the mechanism by which epidermal keratinocytes recognize exogenous stimuli is limited, with transient receptor potential (TRP) channels and olfactory receptor (OR) OR2AT4 having been proposed to serve as receptors for exogenous stimuli in keratinocytes 12,15,16 …”

Section: Introductionmentioning

confidence: 99%

Functionally expressed bitter taste receptor TAS2R14 in human epidermal keratinocytes serves as a chemosensory receptor

Bigliardi

Stelmashenko

et al. 2021

Traditionally, it is theorized that skin sensation is initiated when cutaneous sensory afferents and Merkel cells receive sensory stimuli, while epidermal keratinocytes were deemed to have no role. However, mounting evidence has shown that keratinocytes can initiate skin sensation by receiving sensory stimuli and transmitting sensory information to sensory afferents. Knowledge regarding the mechanisms by which keratinocytes receive exogenous stimuli is limited, with TRP channels and olfactory receptors having been proposed to serve as receptors for exogenous stimuli in keratinocytes. Recently, expression analyses have demonstrated the expression of multiple TAS2R genes in human skin. TAS2Rs are chemosensory GPCRs employed by taste cells to detect bitter‐tasting substances. However, only subtypes TAS2R1 and TAS2R38 have been characterized in epidermal keratinocytes. We present evidence suggesting that subtype TAS2R14 is functionally expressed in epidermal keratinocytes. TAS2R14 transcripts and protein were detected in primary and N/TERT‐1 keratinocytes. Additionally, keratinocytes responded to α‐thujone, a TAS2R14 ligand, with an increase in intracellular free Ca2+ concentration. The tastant‐evoked Ca2+ signals were found to be mediated by wild‐type TAS2R14 and heterotrimeric G proteins. We conclude that TAS2R14 serves as a chemosensory receptor in epidermal keratinocytes and hypothesize that it enables the cells to recognize potentially harmful chemical substances.

“…Unfortunately, the establishment of direct cellular contacts was not investigated in this study . More recently, Krishnan‐Kutty et al have reported that keratinocytes promoted cellular contact with neural crest cells differentiated into sensory neurones, whereas fibroblasts did not. These contradictory results can, in part, be explained by differences in cellular models that need to be better characterized.…”

Section: Pathological Scarringmentioning

confidence: 94%

New insights into the roles of myofibroblasts and innervation during skin healing and innovative therapies to improve scar innervation

Lebonvallet

Laverdet

Miséry

et al. 2018

During the resolution phase of normal skin wound healing, there is a considerable loss of various cell types, including myofibroblasts by apoptosis. Inappropriate delay of apoptosis, and thus increased survival of myofibroblasts, may be a factor leading to pathologies and excessive scarring. Considerable data now clearly suggest that innervation plays a major role in wound healing, including the modulation of fibroblast cellular activity. An abnormal level of neuromediators is implicated not only in the development of chronic wounds but also in excessive scar formation.Understanding interactions between neuromediators and myofibroblasts, allowing normal reinnervation and having adequate levels of neuromediators during the healing process are clearly important to avoid the appearance of pathological healing or fibrosis/scarring. The aim of this review was first to discuss the mechanisms leading to normal or excessive scarring and then to present the roles of innervation during wound healing. Finally, the latest therapeutic strategies to help wound repair and reinnervation after skin damage will be introduced. Advantages and limitations in the use of neuropeptides, growth factors and biomaterials will be discussed as well as the most recent studies on electrostimulation and the potential of targeting resident skin mesenchymal stem cells. K E Y W O R D Sinnervation, myofibroblast, pathological scarring, skin repair, skin-derived precursor | 951LEBONVALLET ET AL.