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:	Wook-Joo Lee, Won-Sik Shim
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	dry skin TSLP TRPV4 keratinocyte sensory neuron mast cell Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/62c9befeced346c1b2a760a18dc8eaa5
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spelling	oai:doaj.org-article:62c9befeced346c1b2a760a18dc8eaa52021-12-02T08:59:59ZCutaneous Neuroimmune Interactions of TSLP and TRPV4 Play Pivotal Roles in Dry Skin-Induced Pruritus1664-322410.3389/fimmu.2021.772941https://doaj.org/article/62c9befeced346c1b2a760a18dc8eaa52021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.772941/fullhttps://doaj.org/toc/1664-3224Dry 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.Wook-Joo LeeWook-Joo LeeWon-Sik ShimWon-Sik ShimFrontiers Media S.A.articledry skinTSLPTRPV4keratinocytesensory neuronmast cellImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	dry skin TSLP TRPV4 keratinocyte sensory neuron mast cell Immunologic diseases. Allergy RC581-607
spellingShingle	dry skin TSLP TRPV4 keratinocyte sensory neuron mast cell Immunologic diseases. Allergy RC581-607 Wook-Joo Lee Wook-Joo Lee Won-Sik Shim Won-Sik Shim Cutaneous Neuroimmune Interactions of TSLP and TRPV4 Play Pivotal Roles in Dry Skin-Induced Pruritus
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.
format	article
author	Wook-Joo Lee Wook-Joo Lee Won-Sik Shim Won-Sik Shim
author_facet	Wook-Joo Lee Wook-Joo Lee Won-Sik Shim Won-Sik Shim
author_sort	Wook-Joo Lee
title	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_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_sort	cutaneous neuroimmune interactions of tslp and trpv4 play pivotal roles in dry skin-induced pruritus
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/62c9befeced346c1b2a760a18dc8eaa5
work_keys_str_mv	AT wookjoolee cutaneousneuroimmuneinteractionsoftslpandtrpv4playpivotalrolesindryskininducedpruritus AT wookjoolee cutaneousneuroimmuneinteractionsoftslpandtrpv4playpivotalrolesindryskininducedpruritus AT wonsikshim cutaneousneuroimmuneinteractionsoftslpandtrpv4playpivotalrolesindryskininducedpruritus AT wonsikshim cutaneousneuroimmuneinteractionsoftslpandtrpv4playpivotalrolesindryskininducedpruritus
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Cutaneous Neuroimmune Interactions of TSLP and TRPV4 Play Pivotal Roles in Dry Skin-Induced Pruritus

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