JAK1 Signaling Is Involved in the Induction of Mechanical Alloknesis in Atopic Dermatitis

TL;DR

This study shows that JAK1 signaling contributes to mechanical alloknesis in atopic dermatitis, and JAK1 inhibitors may help reduce this symptom.

Contribution

The study identifies JAK1 as a key player in mechanical alloknesis in AD, suggesting JAK1-selective inhibitors as a targeted treatment.

Findings

Baricitinib and abrocitinib reduced m-alloknesis in a murine AD model.

AZ960 had no effect on m-alloknesis, indicating JAK1's specific role.

JAK inhibitors did not affect skin barrier or dermatitis severity.

Abstract

Background/Objectives: Mechanical alloknesis (m-alloknesis), the sensation of itch evoked by normally non-pruritic mechanical stimuli, is commonly observed in dry skin-associated conditions, such as xerosis, atopic dermatitis (AD), and psoriasis. Janus kinase (JAK) inhibitors are currently used to treat AD and suppress inflammation and itch. However, their specific roles in the modulation of m-alloknesis remain unclear. Therefore, in this study, we investigated the effects of various oral JAK inhibitors on m-alloknesis using a murine model of AD. Methods: An AD-like phenotype was induced in mice through the repeated topical application of an ointment containing Dermatophagoides farinae (house dust mite) extract. The mice were then orally treated with one of three JAK inhibitors: the JAK1/2 inhibitor baricitinib, the JAK1-selective inhibitor abrocitinib, or the JAK2-selective inhibitor AZ960. M-alloknesis was evaluated by quantifying scratching behavior in response to 30 controlled mechanical stimuli applied to lesional skin. Results: The JAK inhibitor treatments did not affect skin barrier integrity, dermatitis severity, or spontaneous scratching behavior. However, baricitinib and abrocitinib significantly reduced m-alloknesis scores, whereas AZ960 had no effect. Conclusions: These results suggest that JAK1 signaling plays a critical role in the induction of m-alloknesis in AD. Selective JAK1 inhibition is a promising therapeutic strategy for attenuating m-alloknesis and improving quality of life for patients with AD, independent of general skin inflammation and barrier function.

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