疾病
感觉系统
感觉神经元
医学
特应性皮炎
生物
神经科学
免疫学
病理
作者
Anna M. Trier,Madison R. Mack,Avery Fredman,Masato Tamari,Aaron M. Ver Heul,Yue Zhao,Changxiong Guo,Oshri Avraham,Zachary K. Ford,Landon K. Oetjen,Jing Feng,Carina Dehner,Dean W. Coble,Asima Badic,Satoru Joshita,Masato Kubo,Robert W. Gereau,Jennifer Alexander‐Brett,Valeria Cavalli,Steve Davidson,Hongzhen Hu,Qin Liu,Brian Kim
标识
DOI:10.1016/j.jaci.2021.09.014
摘要
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.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.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.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.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.
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