title: Chronic mucocutaneous candidiasis in humans with inborn errors of interleukin-17 immunity.
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.
authors.affiliation: 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. anne.puel@inserm.fr
authors.forename: Anne
authors.initials: A
authors.lastname: Puel
authors.forename: Sophie
authors.initials: S
authors.lastname: Cypowyj
authors.forename: Jacinta
authors.initials: J
authors.lastname: Bustamante
authors.forename: Jill F
authors.initials: JF
authors.lastname: Wright
authors.forename: Luyan
authors.initials: L
authors.lastname: Liu
authors.forename: Hye Kyung
authors.initials: HK
authors.lastname: Lim
authors.forename: Mélanie
authors.initials: M
authors.lastname: Migaud
authors.forename: Laura
authors.initials: L
authors.lastname: Israel
authors.forename: Maya
authors.initials: M
authors.lastname: Chrabieh
authors.forename: Magali
authors.initials: M
authors.lastname: Audry
authors.forename: Matthew
authors.initials: M
authors.lastname: Gumbleton
authors.forename: Antoine
authors.initials: A
authors.lastname: Toulon
authors.forename: Christine
authors.initials: C
authors.lastname: Bodemer
authors.forename: Jamila
authors.initials: J
authors.lastname: El-Baghdadi
authors.forename: Matthew
authors.initials: M
authors.lastname: Whitters
authors.forename: Theresa
authors.initials: T
authors.lastname: Paradis
authors.forename: Jonathan
authors.initials: J
authors.lastname: Brooks
authors.forename: Mary
authors.initials: M
authors.lastname: Collins
authors.forename: Neil M
authors.initials: NM
authors.lastname: Wolfman
authors.forename: Saleh
authors.initials: S
authors.lastname: Al-Muhsen
authors.forename: Miguel
authors.initials: M
authors.lastname: Galicchio
authors.forename: Laurent
authors.initials: L
authors.lastname: Abel
authors.forename: Capucine
authors.initials: C
authors.lastname: Picard
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
mesh_terms: D002176:Candida albicans; D002178:Candidiasis, Chronic Mucocutaneous / Q000235:genetics* / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005799:Genes, Dominant; D005808:Genes, Recessive; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D053722:Receptors, Interleukin-17 / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D058504:Th17 Cells / Q000276:immunology
chemical_list: D020381:Interleukin-17; D053722:Receptors, Interleukin-17