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Cutaneous Neuroimmune Interactions of TSLP and TRPV4 Play Pivotal Roles in Dry Skin-Induced Pruritus

Dry skin is a symptom of skin barrier dysfunction that evokes pruritus; however, the cutaneous neuroimmune interactions underlying dry skin-induced pruritus remain unclear. Therefore, we aimed to elucidate the mechanisms underlying dry skin-induced pruritus. To this end, an acetone/ethanol/water (AE...

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Autores principales: Lee, Wook-Joo, Shim, Won-Sik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8674573/
https://www.ncbi.nlm.nih.gov/pubmed/34925342
http://dx.doi.org/10.3389/fimmu.2021.772941
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author Lee, Wook-Joo
Shim, Won-Sik
author_facet Lee, Wook-Joo
Shim, Won-Sik
author_sort Lee, Wook-Joo
collection PubMed
description Dry skin is a symptom of skin barrier dysfunction that evokes pruritus; however, the cutaneous neuroimmune interactions underlying dry skin-induced pruritus remain unclear. Therefore, we aimed to elucidate the mechanisms underlying dry skin-induced pruritus. To this end, an acetone/ethanol/water (AEW)-induced mouse model of dry skin was used in this study. We observed that the production of thymic stromal lymphopoietin (TSLP) significantly increased in the keratinocytes of AEW mice. Importantly, treatment with an antagonist of transient receptor potential cation channel subfamily V member 4 (TRPV4), HC067047, ameliorated dry skin conditions in AEW mice. The symptoms of dry skin were significantly reduced in Trpv4 knockout (KO) mice following treatment with AEW. The increase in the intracellular calcium levels by TSLP in the dorsal root ganglia (DRG) of Trpv4 KO mice was also significantly attenuated. The spontaneous scratching bouts were significantly decreased in both the HC067047-treated and Trpv4 KO AEW mice. Importantly, the TSLP-dependent release of tryptase from the mast cells was significantly reduced in both the HC067047-treated mice and Trpv4 KO AEW mice. Notably, inhibition of the TSLP-induced signaling pathway in DRG selectively reduced the spontaneous scratching bouts in AEW mice. Overall, the results demonstrated that the cutaneous neuroimmune interactions of TSLP and TRPV4 play pivotal roles in dry skin-induced pruritus.
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spelling pubmed-86745732021-12-17 Cutaneous Neuroimmune Interactions of TSLP and TRPV4 Play Pivotal Roles in Dry Skin-Induced Pruritus Lee, Wook-Joo Shim, Won-Sik Front Immunol Immunology Dry skin is a symptom of skin barrier dysfunction that evokes pruritus; however, the cutaneous neuroimmune interactions underlying dry skin-induced pruritus remain unclear. Therefore, we aimed to elucidate the mechanisms underlying dry skin-induced pruritus. To this end, an acetone/ethanol/water (AEW)-induced mouse model of dry skin was used in this study. We observed that the production of thymic stromal lymphopoietin (TSLP) significantly increased in the keratinocytes of AEW mice. Importantly, treatment with an antagonist of transient receptor potential cation channel subfamily V member 4 (TRPV4), HC067047, ameliorated dry skin conditions in AEW mice. The symptoms of dry skin were significantly reduced in Trpv4 knockout (KO) mice following treatment with AEW. The increase in the intracellular calcium levels by TSLP in the dorsal root ganglia (DRG) of Trpv4 KO mice was also significantly attenuated. The spontaneous scratching bouts were significantly decreased in both the HC067047-treated and Trpv4 KO AEW mice. Importantly, the TSLP-dependent release of tryptase from the mast cells was significantly reduced in both the HC067047-treated mice and Trpv4 KO AEW mice. Notably, inhibition of the TSLP-induced signaling pathway in DRG selectively reduced the spontaneous scratching bouts in AEW mice. Overall, the results demonstrated that the cutaneous neuroimmune interactions of TSLP and TRPV4 play pivotal roles in dry skin-induced pruritus. Frontiers Media S.A. 2021-12-02 /pmc/articles/PMC8674573/ /pubmed/34925342 http://dx.doi.org/10.3389/fimmu.2021.772941 Text en Copyright © 2021 Lee and Shim https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Lee, Wook-Joo
Shim, Won-Sik
Cutaneous Neuroimmune Interactions of TSLP and TRPV4 Play Pivotal Roles in Dry Skin-Induced Pruritus
title Cutaneous Neuroimmune Interactions of TSLP and TRPV4 Play Pivotal Roles in Dry Skin-Induced Pruritus
title_full Cutaneous Neuroimmune Interactions of TSLP and TRPV4 Play Pivotal Roles in Dry Skin-Induced Pruritus
title_fullStr Cutaneous Neuroimmune Interactions of TSLP and TRPV4 Play Pivotal Roles in Dry Skin-Induced Pruritus
title_full_unstemmed Cutaneous Neuroimmune Interactions of TSLP and TRPV4 Play Pivotal Roles in Dry Skin-Induced Pruritus
title_short Cutaneous Neuroimmune Interactions of TSLP and TRPV4 Play Pivotal Roles in Dry Skin-Induced Pruritus
title_sort cutaneous neuroimmune interactions of tslp and trpv4 play pivotal roles in dry skin-induced pruritus
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8674573/
https://www.ncbi.nlm.nih.gov/pubmed/34925342
http://dx.doi.org/10.3389/fimmu.2021.772941
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