RRC ID 82458
Author Lee WJ, Shim WS.
Title Cutaneous Neuroimmune Interactions of TSLP and TRPV4 Play Pivotal Roles in Dry Skin-Induced Pruritus.
Journal Front Immunol
Abstract 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.
Volume 12
Pages 772941
Published 2021-1-1
DOI 10.3389/fimmu.2021.772941
PMID 34925342
PMC PMC8674573
MeSH Animals Cells, Cultured Cytokines / immunology* Ganglia, Spinal Humans Keratinocytes / immunology Male Mast Cells / immunology Mice Mice, Inbred C57BL Mice, Inbred ICR Mice, Knockout Morpholines / pharmacology Neuroimmunomodulation* Neurons / immunology Pruritus / immunology* Pyrroles / pharmacology Skin / immunology* TRPV Cation Channels / antagonists & inhibitors TRPV Cation Channels / genetics TRPV Cation Channels / immunology* Thymic Stromal Lymphopoietin
Resource
Mice RBRC01939