Skin inflammation and itch response are independently regulated by distinct nociceptor subsets
Abstract
Common dermatological disorders are characterized by inflammation and severe itching, which represent a significant clinical challenge. The mechanisms by which nociceptive sensory neurons (nociceptors) integrate peripheral signals to modulate inflammation and itch remain unclear. Here, we showed that two subsets of nociceptors had distinct and nonredundant biological functions in a model of allergic contact dermatitis (ACD). Retrograde axonal tracing of skin-projecting neurons combined with single-cell profiling identified a subset of MrgprD + nonpeptidergic neurons that adopted a transitory regenerative program in response to skin inflammation. Selective ablation of reprogrammed MrgprD + nonpeptidergic neurons during ACDlike inflammation abolished itch-evoked behavior but did not affect skin inflammation. Conversely, selective depletion of Trpv1 + peptidergic neurons exacerbated inflammation through increased neutrophilic infiltration without impacting itch-evoked behavior. This study reveals the presence of two distinct and adaptive neuronal circuits that independently regulate allergic inflammation and itch in the skin.
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BibTeX
@article{voisin2026skin,
title = {{Skin inflammation and itch response are independently regulated by distinct nociceptor subsets}},
author = {Tiphaine Voisin and Nadine Gheziel and Céline El Samrout and Jérémy Martin and Amyaouch Bradaia and Mircea Iftinca and Manon Defaye and Aude Charron and Nasser S Abdullah and Celia Changenot and Anne-Alicia Gonzalez and Antoine Depluech and Elodie Labit and Nathalie Saint-Laurent and Larissa Staurengo-Ferrari and Ozge Erdogan and Marie Tauber and Alexia Loste and Nadine Serhan and Sara Villa-Hernandez and Isaac M Chiu and Aziz Moqrich and Christophe Altier and Lilian Basso and Nicolas Gaudenzio},
journal = {Immunity},
year = {2026},
month = may,
doi = {10.1016/j.immuni.2026.03.020},
url = {https://hal.science/hal-05847975v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Skin inflammation and itch response are independently regulated by distinct nociceptor subsets
AU - Tiphaine Voisin
AU - Nadine Gheziel
AU - Céline El Samrout
AU - Jérémy Martin
AU - Amyaouch Bradaia
AU - Mircea Iftinca
AU - Manon Defaye
AU - Aude Charron
AU - Nasser S Abdullah
AU - Celia Changenot
AU - Anne-Alicia Gonzalez
AU - Antoine Depluech
AU - Elodie Labit
AU - Nathalie Saint-Laurent
AU - Larissa Staurengo-Ferrari
AU - Ozge Erdogan
AU - Marie Tauber
AU - Alexia Loste
AU - Nadine Serhan
AU - Sara Villa-Hernandez
AU - Isaac M Chiu
AU - Aziz Moqrich
AU - Christophe Altier
AU - Lilian Basso
AU - Nicolas Gaudenzio
PY - 2026
DA - 2026/05/12
JO - Immunity
DO - 10.1016/j.immuni.2026.03.020
UR - https://hal.science/hal-05847975v1
AB - Common dermatological disorders are characterized by inflammation and severe itching, which represent a significant clinical challenge. The mechanisms by which nociceptive sensory neurons (nociceptors) integrate peripheral signals to modulate inflammation and itch remain unclear. Here, we showed that two subsets of nociceptors had distinct and nonredundant biological functions in a model of allergic contact dermatitis (ACD). Retrograde axonal tracing of skin-projecting neurons combined with single-cell profiling identified a subset of MrgprD + nonpeptidergic neurons that adopted a transitory regenerative program in response to skin inflammation. Selective ablation of reprogrammed MrgprD + nonpeptidergic neurons during ACDlike inflammation abolished itch-evoked behavior but did not affect skin inflammation. Conversely, selective depletion of Trpv1 + peptidergic neurons exacerbated inflammation through increased neutrophilic infiltration without impacting itch-evoked behavior. This study reveals the presence of two distinct and adaptive neuronal circuits that independently regulate allergic inflammation and itch in the skin.
SN - 1074-7613
ER -