Traditionally, peripheral sensory neurons are assumed as the exclusive transducers of external stimuli. Current research moves epidermal keratinocytes into focus as sensors and transmitters of nociceptive and non-nociceptive sensations, tightly interacting with intraepidermal nerve fibers at the neuro-cutaneous unit. In animal models, epidermal cells establish close contacts and ensheath sensory neurites. However, ultrastructural morphological and mechanistic data examining the human keratinocyte-nerve fiber interface are sparse. We investigated this exact interface in human skin applying super-resolution array tomography, expansion microscopy, and structured illumination microscopy. We show keratinocyte ensheathment of afferents and adjacent connexin 43 contacts in native skin and have applied a pipeline based on expansion microscopy to quantify these parameter in skin sections of healthy participants versus patients with small fiber neuropathy. We further derived a fully human co-culture system, visualizing ensheathment and connexin 43 plaques in vitro. Unraveling human intraepidermal nerve fiber ensheathment and potential interaction sites advances research at the neuro-cutaneous unit. These findings are crucial on the way to decipher the mechanisms of cutaneous nociception.
%0 Journal Article
%1 10.7554/eLife.77761
%A Erbacher, Christoph
%A Britz, Sebastian
%A Dinkel, Philine
%A Klein, Thomas
%A Sauer, Markus
%A Stigloher, Christian
%A Üçeyler, Nurcan
%D 2024
%E Chesler, Alexander Theodore
%E Swartz, Kenton J
%E Albers, Kathryn M
%E Price, Theodore J
%I eLife Sciences Publications, Ltd
%J eLife
%K myown stigloher_high zam
%P e77761
%R 10.7554/eLife.77761
%T Interaction of human keratinocytes and nerve fiber terminals at the neuro-cutaneous unit
%U https://doi.org/10.7554/eLife.77761
%V 13
%X Traditionally, peripheral sensory neurons are assumed as the exclusive transducers of external stimuli. Current research moves epidermal keratinocytes into focus as sensors and transmitters of nociceptive and non-nociceptive sensations, tightly interacting with intraepidermal nerve fibers at the neuro-cutaneous unit. In animal models, epidermal cells establish close contacts and ensheath sensory neurites. However, ultrastructural morphological and mechanistic data examining the human keratinocyte-nerve fiber interface are sparse. We investigated this exact interface in human skin applying super-resolution array tomography, expansion microscopy, and structured illumination microscopy. We show keratinocyte ensheathment of afferents and adjacent connexin 43 contacts in native skin and have applied a pipeline based on expansion microscopy to quantify these parameter in skin sections of healthy participants versus patients with small fiber neuropathy. We further derived a fully human co-culture system, visualizing ensheathment and connexin 43 plaques in vitro. Unraveling human intraepidermal nerve fiber ensheathment and potential interaction sites advances research at the neuro-cutaneous unit. These findings are crucial on the way to decipher the mechanisms of cutaneous nociception.
@article{10.7554/eLife.77761,
abstract = {Traditionally, peripheral sensory neurons are assumed as the exclusive transducers of external stimuli. Current research moves epidermal keratinocytes into focus as sensors and transmitters of nociceptive and non-nociceptive sensations, tightly interacting with intraepidermal nerve fibers at the neuro-cutaneous unit. In animal models, epidermal cells establish close contacts and ensheath sensory neurites. However, ultrastructural morphological and mechanistic data examining the human keratinocyte-nerve fiber interface are sparse. We investigated this exact interface in human skin applying super-resolution array tomography, expansion microscopy, and structured illumination microscopy. We show keratinocyte ensheathment of afferents and adjacent connexin 43 contacts in native skin and have applied a pipeline based on expansion microscopy to quantify these parameter in skin sections of healthy participants versus patients with small fiber neuropathy. We further derived a fully human co-culture system, visualizing ensheathment and connexin 43 plaques in vitro. Unraveling human intraepidermal nerve fiber ensheathment and potential interaction sites advances research at the neuro-cutaneous unit. These findings are crucial on the way to decipher the mechanisms of cutaneous nociception.},
added-at = {2024-02-09T13:12:48.000+0100},
article_type = {journal},
author = {Erbacher, Christoph and Britz, Sebastian and Dinkel, Philine and Klein, Thomas and Sauer, Markus and Stigloher, Christian and Üçeyler, Nurcan},
biburl = {https://www.bibsonomy.org/bibtex/284ceef8faf0b2a4953e3099bdf46a9de/zam},
citation = {eLife 2024;13:e77761},
doi = {10.7554/eLife.77761},
editor = {Chesler, Alexander Theodore and Swartz, Kenton J and Albers, Kathryn M and Price, Theodore J},
interhash = {5addbc4186219019972e646513f05816},
intrahash = {84ceef8faf0b2a4953e3099bdf46a9de},
issn = {2050-084X},
journal = {eLife},
keywords = {myown stigloher_high zam},
month = jan,
pages = {e77761},
pub_date = {2024-01-16},
publisher = {eLife Sciences Publications, Ltd},
timestamp = {2024-02-09T13:12:48.000+0100},
title = {Interaction of human keratinocytes and nerve fiber terminals at the neuro-cutaneous unit},
url = {https://doi.org/10.7554/eLife.77761},
volume = 13,
year = 2024
}