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Science 332 (6025): 65-68

Copyright © 2011 by the American Association for the Advancement of Science

Chronic Mucocutaneous Candidiasis in Humans with Inborn Errors of Interleukin-17 Immunity

Anne Puel,1,*,{ddagger} Sophie Cypowyj,2,* Jacinta Bustamante,1 Jill F. Wright,3 Luyan Liu,1 Hye Kyung Lim,2 Mélanie Migaud,1 Laura Israel,1 Maya Chrabieh,1 Magali Audry,2 Matthew Gumbleton,4 Antoine Toulon,5 Christine Bodemer,5 Jamila El-Baghdadi,6 Matthew Whitters,3 Theresa Paradis,3 Jonathan Brooks,3 Mary Collins,3 Neil M. Wolfman,3 Saleh Al-Muhsen,7 Miguel Galicchio,8 Laurent Abel,1,2,{dagger} Capucine Picard,1,9,10,{dagger} Jean-Laurent Casanova1,2,7,10,{ddagger}

Abstract: Chronic mucocutaneous candidiasis disease (CMCD) is characterized by recurrent or persistent infections of the skin, nails, and oral and genital mucosae caused by Candida albicans and, to a lesser extent, Staphylococcus aureus, in patients with no other infectious or autoimmune manifestations. We report two genetic etiologies of CMCD: autosomal recessive deficiency in the cytokine receptor, interleukin-17 receptor A (IL-17RA), and autosomal dominant deficiency of the cytokine interleukin-17F (IL-17F). IL-17RA deficiency is complete, abolishing cellular responses to IL-17A and IL-17F homo- and heterodimers. By contrast, IL-17F deficiency is partial, with mutant IL-17F–containing homo- and heterodimers displaying impaired, but not abolished, activity. These experiments of nature indicate that human IL-17A and IL-17F are essential for mucocutaneous immunity against C. albicans, but otherwise largely redundant.

1 Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale, U980, and University Paris Descartes, Necker Medical School, 75015 Paris, France.
2 St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065, USA.
3 Inflammation and Immunology, Pfizer Research, Cambridge, MA 02140, USA.
4 SUNY Upstate Medical University, Syracuse, NY 13210, USA.
5 Dermatology Unit, Necker Hospital, 75015 Paris, France.
6 Unit of Genetics, Military Hospital of Instruction Mohamed V, Rabat 10000, Morocco.
7 Prince Naif Center for Immunology Research, Department of Pediatrics, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia.
8 Victor J. Vilela Children’s Hospital, Rosario, Santa Fe 2000, Argentina.
9 Center for the Study of Primary Immunodeficiencies, Necker Hospital, 75015 Paris, France.
10 Pediatric Hematology-Immunology Unit, Necker Hospital, Paris 75015, France.

* These authors contributed equally to this work.

{dagger} These authors contributed equally to this work.

{ddagger} To whom correspondence should be addressed. E-mail: jean-laurent.casanova{at} (J.-L.C.); anne.puel{at} (A.P.)

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