Epidermal Langerhans Cells Act as Neuroimmune Regulators of Pain and Itch
- 1University of Miami Miller School of Medicine
Abstract
Neuroimmune interactions in the skin coordinate immune defense and somatosensory perception, yet how immune cells shape sensory signaling remains poorly defined. Here, we show that Langerhans cells (LCs), epidermal antigen-presenting cells, function as local immune-derived amplifiers of cutaneous sensory signaling. Anatomical and transcriptomic analyses reveal preferential LC association with non-peptidergic sensory neurons. LC activation increases neuronal and behavioral responses to thermal, mechanical, and pruritic stimuli without directly exciting sensory neurons, whereas LC inhibition or ablation selectively reduces pruritogen-evoked itch. We identified semaphorin 7A as a candidate LC-expressed mediator. Semaphorin 7A sensitized cultured sensory neurons to chloroquine and histamine, and neutralizing semaphorin 7A abolished the increase in chloroquine-evoked scratching produced by LC activation. Its receptor PlexinC1 was expressed by most MrgprA3 pruriceptors and blocking PlexinC1 reduced semaphorin 7A-evoked neuronal responses. Together, these findings identify epidermal LCs as local immune-derived amplifiers that regulate the responsiveness of cutaneous sensory circuits and identify semaphorin 7A as a mediator of LC-induced itch potentiation.
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BibTeX
@misc{sakai2026epidermal,
title = {{Epidermal Langerhans Cells Act as Neuroimmune Regulators of Pain and Itch}},
author = {K. Sakai and H. Ishida and D. Pavlenko and M. Suehiro and T. Oshea and J. Dorning and K. Sanders and C. Sanchez and A. Lopez and S. Talamas and M. Boulina and A. J. Griswold and T. Akiyama},
howpublished = {bioRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.06.756111},
url = {https://www.biorxiv.org/content/10.64898/2026.11.06.756111v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Epidermal Langerhans Cells Act as Neuroimmune Regulators of Pain and Itch
AU - K. Sakai
AU - H. Ishida
AU - D. Pavlenko
AU - M. Suehiro
AU - T. Oshea
AU - J. Dorning
AU - K. Sanders
AU - C. Sanchez
AU - A. Lopez
AU - S. Talamas
AU - M. Boulina
AU - A. J. Griswold
AU - T. Akiyama
PY - 2026
DA - 2026/11/06
PB - bioRxiv
DO - 10.64898/2026.11.06.756111
UR - https://www.biorxiv.org/content/10.64898/2026.11.06.756111v1
AB - Neuroimmune interactions in the skin coordinate immune defense and somatosensory perception, yet how immune cells shape sensory signaling remains poorly defined. Here, we show that Langerhans cells (LCs), epidermal antigen-presenting cells, function as local immune-derived amplifiers of cutaneous sensory signaling. Anatomical and transcriptomic analyses reveal preferential LC association with non-peptidergic sensory neurons. LC activation increases neuronal and behavioral responses to thermal, mechanical, and pruritic stimuli without directly exciting sensory neurons, whereas LC inhibition or ablation selectively reduces pruritogen-evoked itch. We identified semaphorin 7A as a candidate LC-expressed mediator. Semaphorin 7A sensitized cultured sensory neurons to chloroquine and histamine, and neutralizing semaphorin 7A abolished the increase in chloroquine-evoked scratching produced by LC activation. Its receptor PlexinC1 was expressed by most MrgprA3 pruriceptors and blocking PlexinC1 reduced semaphorin 7A-evoked neuronal responses. Together, these findings identify epidermal LCs as local immune-derived amplifiers that regulate the responsiveness of cutaneous sensory circuits and identify semaphorin 7A as a mediator of LC-induced itch potentiation.
ER -