Journal
JOURNAL OF INVESTIGATIVE DERMATOLOGY
Volume 140, Issue 6, Pages 1244-+Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jid.2019.10.022
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Funding
- Doris Duke Charitable Foundation
- Celgene Corporation
- National Institute of Arthritis Musculoskeletal and Skin Diseases of the National Institutes of Health (NIH) [NIH (K08AR065577), NIH (R01AR070116)]
- NIH National Institute of Allergy and Infectious Diseases [T325T32AI00716340]
- NIH National Heart, Lung, and Blood Institute [T32 HL007317]
- Brain Research Foundation Fay/Frank Seed Grant
- Pew Scholar Award
- CSD Consortium [U01HG004080, U42RR024244]
- NIH [U01HG004085]
- CHORI [U42RR024244]
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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 ADassociated 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.
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