{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Trier AM"],"funding":["NEI NIH HHS","NIDDK NIH HHS","Doris Duke Charitable Foundation","NIAID NIH HHS","NHLBI NIH HHS","NIAAA NIH HHS","NCI NIH HHS","NINDS NIH HHS","National Institutes of Health","NIAMS NIH HHS"],"pagination":["1473-1480.e6"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8934751"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["149(4)"],"pubmed_abstract":["<h4>Background</h4>Chronic pruritus, or itch, is common and debilitating, but the neuroimmune mechanisms that drive chronic itch are only starting to be elucidated. Recent studies demonstrate that the IL-33 receptor (IL-33R) is expressed by sensory neurons. However, whether sensory neuron-restricted activity of IL-33 is necessary for chronic itch remains poorly understood.<h4>Objectives</h4>We sought to determine if IL-33 signaling in sensory neurons is critical for the development of chronic itch in 2 divergent pruritic disease models.<h4>Methods</h4>Plasma levels of IL-33 were assessed in patients with atopic dermatitis (AD) and chronic pruritus of unknown origin (CPUO). Mice were generated to conditionally delete IL-33R from sensory neurons. The contribution of neuronal IL-33R signaling to chronic itch development was tested in mouse models that recapitulate key pathologic features of AD and CPUO, respectively.<h4>Results</h4>IL-33 was elevated in both AD and CPUO as well as their respective mouse models. While neuron-restricted IL-33R signaling was dispensable for itch in AD-like disease, it was required for the development of dry skin itch in a mouse model that mirrors key aspects of CPUO pathology.<h4>Conclusions</h4>These data highlight how IL-33 may be a predominant mediator of itch in certain contexts, depending on the tissue microenvironment. Further, this study provides insight into future therapeutic strategies targeting the IL-33 pathway for chronic itch."],"journal":["The Journal of allergy and clinical immunology"],"pubmed_title":["IL-33 signaling in sensory neurons promotes dry skin itch."],"pmcid":["PMC8934751"],"funding_grant_id":["R01 AR077183","F30 AI154912","R01 HL152245","T32 HL007317","R01 EY024704","R21 AI167047","P30 DK052574","R01 NS111719","R01 AA027065","P30 CA091842","RF1 NS113881","K08 AR065577","T32 AI007163","R01 NS042595","R01 DK103901","R01 AI125743","2016104","R01 AR077007","R01 AI163146","R01 AR070116"],"pubmed_authors":["Avraham O","Oetjen LK","Mack MR","Joshita S","Ford ZK","Davidson S","Liu Q","Alexander-Brett J","Trier AM","Guo CJ","Dehner C","Tamari M","Zhao Y","Coble D","Ver Heul AM","Badic A","Cavalli V","Fredman A","Feng J","Hu H","Kim BS","Gereau RW","Kubo M"],"additional_accession":[]},"is_claimable":false,"name":"IL-33 signaling in sensory neurons promotes dry skin itch.","description":"<h4>Background</h4>Chronic pruritus, or itch, is common and debilitating, but the neuroimmune mechanisms that drive chronic itch are only starting to be elucidated. Recent studies demonstrate that the IL-33 receptor (IL-33R) is expressed by sensory neurons. However, whether sensory neuron-restricted activity of IL-33 is necessary for chronic itch remains poorly understood.<h4>Objectives</h4>We sought to determine if IL-33 signaling in sensory neurons is critical for the development of chronic itch in 2 divergent pruritic disease models.<h4>Methods</h4>Plasma levels of IL-33 were assessed in patients with atopic dermatitis (AD) and chronic pruritus of unknown origin (CPUO). Mice were generated to conditionally delete IL-33R from sensory neurons. The contribution of neuronal IL-33R signaling to chronic itch development was tested in mouse models that recapitulate key pathologic features of AD and CPUO, respectively.<h4>Results</h4>IL-33 was elevated in both AD and CPUO as well as their respective mouse models. While neuron-restricted IL-33R signaling was dispensable for itch in AD-like disease, it was required for the development of dry skin itch in a mouse model that mirrors key aspects of CPUO pathology.<h4>Conclusions</h4>These data highlight how IL-33 may be a predominant mediator of itch in certain contexts, depending on the tissue microenvironment. Further, this study provides insight into future therapeutic strategies targeting the IL-33 pathway for chronic itch.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Apr","modification":"2026-05-09T23:43:16.822Z","creation":"2025-04-04T22:13:18.571Z"},"accession":"S-EPMC8934751","cross_references":{"pubmed":["34560104"],"doi":["10.1016/j.jaci.2021.09.014"]}}