Interleukin-31-mediated photoablation of pruritogenic epidermal neurons reduces itch-associated behaviours in mice.,Nature Biomedical Engineering

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Interleukin-31-mediated photoablation of pruritogenic epidermal neurons reduces itch-associated behaviours in mice.
Nature Biomedical Engineering ( IF 26.8 ) Pub Date : 2018-12-17 , DOI: 10.1038/s41551-018-0328-5
Linda Nocchi _{1,

2} , Nainika Roy ₁ , Mariangela D'Attilia ₁ , Rahul Dhandapani _{1,

2} , Mariano Maffei _{1,

2} , Andrei Traista ₁ , Laura Castaldi _{1,

2} , Emerald Perlas ₁ , Cora Hallie Chadick ₁ , Paul A Heppenstall _{1,

2}

Affiliation

Itch-a major symptom of many chronic skin diseases-can exacerbate inflammation by provoking scratching and subsequent skin damage. Here, we show that activation, via near infrared illumination, of a phototoxic agent that selectively targets itch-sensing cells can reduce itch-associated behaviours in mice. We generated a SNAP-tagged interleukin-31 (IL-31) ligand derivative (IL-31K138A-SNAP) that selectively binds receptors on itch-associated cells, without evoking IL-31-receptor signalling or scratching, and conjugated it to the photosensitizer IRDye 700DX phthalocyanine. Subcutaneous injection of IL-31K138A-SNAP-IR700 in mice followed by near infrared illumination resulted in the long-term reversal of the scratching behaviour evoked by the pruritogenic IL-31, an effect that was associated with the selective retraction of itch-sensing neurons in the skin. We also show that a topical preparation of IL-31K138A-SNAP-IR700 reversed the behavioural and dermatological indicators of disease in mouse models of atopic dermatitis and of the genetic skin disease familial primary localized cutaneous amyloidosis. Targeted photoablation may enable itch control for the treatment of inflammatory skin diseases.

中文翻译：

白细胞介素 31 介导的致痒表皮神经元光消融减少了小鼠的瘙痒相关行为。

瘙痒——许多慢性皮肤病的主要症状——会通过引起抓挠和随后的皮肤损伤来加剧炎症。在这里，我们展示了通过近红外照明激活选择性靶向瘙痒感应细胞的光毒剂可以减少小鼠与瘙痒相关的行为。我们生成了一种 SNAP 标记的白细胞介素 31 (IL-31) 配体衍生物 (IL-31K138A-SNAP)，它选择性地结合瘙痒相关细胞上的受体，而不引起 IL-31 受体信号传导或刮擦，并将其与光敏剂结合IRDye 700DX 酞菁。在小鼠中皮下注射 IL-31K138A-SNAP-IR700，然后进行近红外照射，可长期逆转由致痒性 IL-31 引起的搔抓行为，这种效应与皮肤中瘙痒感应神经元的选择性收缩有关。我们还表明，IL-31K138A-SNAP-IR700 的局部制剂逆转了特应性皮炎和遗传性皮肤病家族性原发性局部皮肤淀粉样变性小鼠模型中疾病的行为和皮肤病学指标。靶向光消融可以控制瘙痒以治疗炎症性皮肤病。

更新日期：2019-01-26

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