The Journal of allergy and clinical immunology · 2022
Mechanistic insights into the antipruritic effects of lebrikizumab, an anti-IL-13 mAb.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Miron Yannick, Miller Paul E, Hughes Chloe, Indersmitten Tim, Lerner Ethan A, Cevikbas Ferda
Аннотация
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.
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.