Original Article
Itch
Kallikrein 7 Promotes Atopic Dermatitis-Associated Itch Independently of Skin Inflammation

https://doi.org/10.1016/j.jid.2019.10.022Get rights and content
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Atopic dermatitis (AD) is a highly prevalent, itchy inflammatory skin disorder that is thought to arise from a combination of skin barrier defect and immune dysregulation. Kallikreins (KLK), a family of serine proteases with a diverse array of homeostatic functions, including skin desquamation and innate immunity, are hypothesized to contribute to AD pathogenesis. However, their precise role in AD has not been clearly defined. In this study, RNA sequencing analyses identified KLK7 as the most abundant and differentially expressed KLK in both human AD and murine AD-like skin. Further, in mice, Klk7 expression was localized to the epidermis in both steady state and inflammation. Unexpectedly, KLK7 was dispensable for the development of AD-associated skin inflammation. Instead, KLK7 was selectively required for AD-associated chronic itch. Even without the alleviation of skin inflammation, KLK7-deficient mice exhibited significantly attenuated scratching, compared with littermate controls, after AD-like disease induction. Collectively, our findings indicate that KLK7 promotes AD-associated itch independently from skin inflammation and reveal a previously unrecognized epidermal-neural mechanism of AD associated itch.

Abbreviations

AD
atopic dermatitis
DRG
dorsal root ganglia
KLK
kallikrein
MC903
calcipotriol
PFA
paraformaldehyde
RNA-Seq
RNA sequencing
RT-qPCR
quantitative reverse transcriptase–PCR

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These authors contributed equally to this work.