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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred


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Volume 395, Issue 9

Issues

Netherton syndrome: defective kallikrein inhibition in the skin leads to skin inflammation and allergy

Laetitia Furio
  • University Paris Descartes, Sorbonne Paris Cité, Paris, France
  • INSERM UMR 1163, Laboratory of Genetic skin diseases, Imagine Institute, 24 boulevard Montparnasse, F-7505 Paris, France
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Alain Hovnanian
  • Corresponding author
  • University Paris Descartes, Sorbonne Paris Cité, Paris, France
  • INSERM UMR 1163, Laboratory of Genetic skin diseases, Imagine Institute, 24 boulevard Montparnasse, F-7505 Paris, France
  • Department of Genetics, Paris, France
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2014-08-06 | DOI: https://doi.org/10.1515/hsz-2014-0137

Abstract

Netherton syndrome (NS) is an orphan genetic skin disease with a profound skin barrier defect and severe allergic manifestations. NS is caused by loss of function mutations in SPINK5 encoding lympho-epithelial Kazal-type inhibitor (LEKTI), a secreted multi-domain serine protease inhibitor expressed in stratified epithelia. Studies in mouse models and in NS patients have established that unopposed kallikrein 5 activity triggers stratum corneum detachment and activates PAR-2 signaling, leading to the autonomous production of pro-allergic and pro-inflammatory mediators. This emerging knowledge on NS pathogenesis has highlighted a central role for protease regulation in skin homeostasis but also in the complexity of the disease, and holds the promise of new specific treatments.

Keywords: allergy; kallikrein; Netherton syndrome; skin inflammation

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About the article

Laetitia Furio

Laetitia Furio is a post-doctoral fellow at University Paris Descartes-Paris Sorbonne Cité at Imagine Institute in Paris, France. She completed her PhD on cutaneous immunology in 2008. In 2010, she joined Alain Hovnanian’s group to work on a severe genetic skin disease called Netherton syndrome (NS). To better understand NS pathophysiology, she has been developing and characterizing several new murine models for NS and has performed detailed clinical and biological investigations of a large cohort of NS patients.

Alain Hovnanian

Alain Hovnanian is full professor of Dermatology and Genetics at the new ‘Institut Hospitalo-Universitaire’ (IHU) at Necker hospital in Paris. He runs a translational clinic on genetic skin diseases of children and adults at Necker hospital for Sick Children. He is the director of a diagnostic and research laboratory at INSERM UMR 1163 on genetic skin diseases at the Imagine Institute for genetic diseases.The central theme of his research. is the development of translational research to improve the understanding and treatment of severe genetic skin diseases. Following the identification of the SPINK5 gene encoding the LEKTI protease inhibitor as the defective gene in Netherton syndrome (NS), his group has developed several murine models for NS in order to dissect the roles of proteases and their inhibitors in the biological cascades involved in the disease. This work has placed epidermal kallikreins at the center of skin inflammation and allergy in NS and has led to the identification of new therapeutic targets. Currently, his research aims at improving our understanding on NS and other inflammatory skin diseases in order to design innovative and efficient therapies. He has published over 200 research articles, review articles and book chapters. Photograph: Copyright © Laurent Attias/Fondation Imagine.


Corresponding author: Alain Hovnanian, University Paris Descartes, Sorbonne Paris Cité, Paris, France; INSERM UMR 1163, Laboratory of Genetic skin diseases, Imagine Institute, 24 boulevard Montparnasse, F-7505 Paris, France; and Department of Genetics, Paris, France, e-mail:


Received: 2014-02-15

Accepted: 2014-06-06

Published Online: 2014-08-06

Published in Print: 2014-09-01


Citation Information: Biological Chemistry, Volume 395, Issue 9, Pages 945–958, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/hsz-2014-0137.

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