AnaBios Corporation, San Diego, Calif.
Massachusetts General Hospital/Harvard Medical School, Boston, Mass.
J Allergy Clin Immunol. 2022 Sep;150(3):690-700. doi: 10.1016/j.jaci.2022.01.028. Epub 2022 Mar 1.
Atopic dermatitis is a chronic inflammatory skin disease with persistent and severe itch among its hallmark features. Significant increases in type 2 cytokines (ie, IL-4, IL-13, IL-31) have been documented in acute atopic dermatitis lesions and lead to multifaceted downstream effects, including inflammation, epidermal barrier dysfunction, and itch.
The primary objective of preclinical studies reported here was to test direct effects of IL-13 and an anti-IL-13 mAb, lebrikizumab, in a human dorsal root ganglion model in itch amplification, neuronal excitability, and transcriptional downstream targets.
Neuroactive effects were assessed via live cell calcium imaging, electric field stimulation, and RNA sequencing of human dorsal root ganglia stimulated with IL-13 alone or in combination with lebrikizumab.
These preclinical findings suggest that IL-13 plays a direct enhancer role in multiple itch and neuroactive pathways as well as transcriptional downstream effects, and provide key insights into the mechanistic basis for lebrikizumab's anti-itch effects.
IL-13 is a potent enhancer of neuronal responses to different itch stimuli, consistent with the neuroimmune axis contributing to chronic itch-associated inflammatory skin disease, and blockade of this cytokine pathway may provide a therapeutic approach.
特应性皮炎是一种慢性炎症性皮肤病，其特征之一是持续且剧烈的瘙痒。在急性特应性皮炎病变中，已记录到 2 型细胞因子（即 IL-4、IL-13、IL-31）的显著增加，导致多方面的下游效应，包括炎症、表皮屏障功能障碍和瘙痒。
本文报告的临床前研究的主要目的是测试 IL-13 和抗 IL-13 mAb（lebrikizumab）在人类背根神经节模型中对瘙痒放大、神经元兴奋性和转录下游靶标直接作用。
通过活细胞钙成像、电场刺激和 RNA 测序评估单独使用 IL-13 或与 lebrikizumab 联合刺激人背根神经节的神经活性效应。
这些临床前发现表明，IL-13 在多种瘙痒和神经活性途径以及转录下游效应中发挥直接增强作用，并为 lebrikizumab 抗瘙痒作用的机制基础提供了重要见解。
IL-13 是神经元对不同瘙痒刺激反应的有效增强剂，与神经免疫轴有助于慢性瘙痒相关炎症性皮肤病一致，阻断该细胞因子途径可能提供一种治疗方法。
