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Publication : Interleukin-31-mediated photoablation of pruritogenic epidermal neurons reduces itch-associated behaviours in mice.

First Author  Nocchi L Year  2019
Journal  Nat Biomed Eng Volume  3
Issue  2 Pages  114-125
PubMed ID  30944432 Mgi Jnum  J:277431
Mgi Id  MGI:6330954 Doi  10.1038/s41551-018-0328-5
Citation  Nocchi L, et al. (2019) Interleukin-31-mediated photoablation of pruritogenic epidermal neurons reduces itch-associated behaviours in mice. Nat Biomed Eng 3(2):114-125
abstractText  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-31(K138A-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-31(K138A-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-31(K138A-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.
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