PT  - JOURNAL ARTICLE
AU  - Christoph Erbacher
AU  - Sebastian Britz
AU  - Philine Dinkel
AU  - Thomas Klein
AU  - Markus Sauer
AU  - Christian Stigloher
AU  - Nurcan Üçeyler
TI  - Interaction of human keratinocytes and nerve fiber terminals at the neuro-cutaneous unit
AID  - 10.1101/2022.02.23.481592
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.02.23.481592
4099  - http://biorxiv.org/content/early/2022/02/26/2022.02.23.481592.short
4100  - http://biorxiv.org/content/early/2022/02/26/2022.02.23.481592.full
AB  - Traditionally, peripheral sensory neurons hold the monopole of transducing 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-nociceptor 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 nociceptors and connexin 43 plaques at keratinocyte-nociceptor contact sites in healthy native skin. We further derived a fully human co-culture system, modeling ensheathment and connexin 43 plaques in vitro. Unraveling human intraepidermal nerve fiber ensheathment and interaction sites marks a milestone in research at the neuro-cutaneous unit. These findings are mind-changers on the way to decipher the mechanisms of cutaneous nociception.Competing Interest StatementThe authors have declared no competing interest.