期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 150, 期 3, 页码 690-700出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2022.01.028
关键词
IL-13; lebrikizumab; atopic dermatitis; itch
资金
- Dermira
These preclinical findings indicate that IL-13 plays a direct enhancer role in multiple itch and neuroactive pathways as well as transcriptional downstream effects, providing insights into the mechanistic basis for lebrikizumab's anti-itch effects.
Background: 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. Objective: 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. Methods: 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. Results: 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. Conclusion: 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.
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