Inherited IL-17RC deficiency in patients with chronic mucocutaneous candidiasis.
Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent or persistent infections of the skin, nail, oral, and genital mucosae with Candida species, mainly C. albicans. Autosomal-recessive (AR) IL-17RA and ACT1 deficiencies and autosomal-dominant IL-17F deficiency, each reported in a single kindred, underlie CMC in otherwise healthy patients. We report three patients from unrelated kindreds, aged 8, 12, and 37 yr with isolated CMC, who display AR IL-17RC deficiency. The patients are homozygous for different nonsense alleles that prevent the expression of IL-17RC on the cell surface. The defect is complete, abolishing cellular responses to IL-17A and IL-17F homo- and heterodimers. However, in contrast to what is observed for the IL-17RA- and ACT1-deficient patients tested, the response to IL-17E (IL-25) is maintained in these IL-17RC-deficient patients. These experiments of nature indicate that human IL-17RC is essential for mucocutaneous immunity to C. albicans but is otherwise largely redundant.
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, French Institute of Health and Medical Research (INSERM) U1163, 75015 Paris, France Imagine Institute, Paris Descartes University, 75015 Paris, France.
Yun
Y
Ling
St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065.
Sophie
S
Cypowyj
Department of Pediatric Immunology, Dr. Sami Ulus Maternity and Children's Health and Diseases Training and Research Hospital, 06080 Ankara, Turkey.
Caner
C
Aytekin
Victor J. Vilela Children's Hospital, Rosario, 2000 Santa Fe, Argentina.
Miguel
M
Galicchio
Division of Infectious Diseases, Clinical Immunology, and Allergy, Department of Pediatrics, Cerrahpaşa Medical Faculty, Istanbul University, 34452 Istanbul, Turkey.
Yildiz
Y
Camcioglu
Division of Infectious Diseases, Clinical Immunology, and Allergy, Department of Pediatrics, Cerrahpaşa Medical Faculty, Istanbul University, 34452 Istanbul, Turkey.
Serdar
S
Nepesov
Department of Pediatric Immunology and Allergy, Ankara University School of Medicine, 06100 Ankara, Turkey.
Aydan
A
Ikinciogullari
Department of Pediatric Immunology and Allergy, Ankara University School of Medicine, 06100 Ankara, Turkey.
Figen
F
Dogu
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, French Institute of Health and Medical Research (INSERM) U1163, 75015 Paris, France Imagine Institute, Paris Descartes University, 75015 Paris, France.
Aziz
A
Belkadi
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, French Institute of Health and Medical Research (INSERM) U1163, 75015 Paris, France Imagine Institute, Paris Descartes University, 75015 Paris, France.
Romain
R
Levy
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, French Institute of Health and Medical Research (INSERM) U1163, 75015 Paris, France Imagine Institute, Paris Descartes University, 75015 Paris, France.
Mélanie
M
Migaud
St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065.
Bertrand
B
Boisson
St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065.
Alexandre
A
Bolze
St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065.
Yuval
Y
Itan
Imagine Institute, Paris Descartes University, 75015 Paris, France UMS24, Cell Imaging Platform, Federative Structure of Research (SFR), Pediatric Hematology-Immunology Unit, and Center for the Study of Primary Immunodeficiencies, Necker Hospital for Sick Children, 75015 Paris, France.
Nicolas
N
Goudin
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, French Institute of Health and Medical Research (INSERM) U1163, 75015 Paris, France Imagine Institute, Paris Descartes University, 75015 Paris, France.
Julien
J
Cottineau
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, French Institute of Health and Medical Research (INSERM) U1163, 75015 Paris, France Imagine Institute, Paris Descartes University, 75015 Paris, France St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065 UMS24, Cell Imaging Platform, Federative Structure of Research (SFR), Pediatric Hematology-Immunology Unit, and Center for the Study of Primary Immunodeficiencies, Necker Hospital for Sick Children, 75015 Paris, France.
Capucine
C
Picard
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, French Institute of Health and Medical Research (INSERM) U1163, 75015 Paris, France Imagine Institute, Paris Descartes University, 75015 Paris, France St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065.
Laurent
L
Abel
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, French Institute of Health and Medical Research (INSERM) U1163, 75015 Paris, France Imagine Institute, Paris Descartes University, 75015 Paris, France St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065 UMS24, Cell Imaging Platform, Federative Structure of Research (SFR), Pediatric Hematology-Immunology Unit, and Center for the Study of Primary Immunodeficiencies, Necker Hospital for Sick Children, 75015 Paris, France.
Jacinta
J
Bustamante
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, French Institute of Health and Medical Research (INSERM) U1163, 75015 Paris, France Imagine Institute, Paris Descartes University, 75015 Paris, France St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065 UMS24, Cell Imaging Platform, Federative Structure of Research (SFR), Pediatric Hematology-Immunology Unit, and Center for the Study of Primary Immunodeficiencies, Necker Hospital for Sick Children, 75015 Paris, France Howard Hughes Medical Institute, New York, NY 10065.
Jean-Laurent
JL
Casanova
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, French Institute of Health and Medical Research (INSERM) U1163, 75015 Paris, France Imagine Institute, Paris Descartes University, 75015 Paris, France St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065 anne.puel@inserm.fr.
Anne
A
Puel
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D002176:Candida albicans / Q000276:immunology*; D002178:Candidiasis, Chronic Mucocutaneous / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D002648:Child; D005260:Female; D006720:Homozygote; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology; D008297:Male; D018123:Receptors, Interleukin / Q000172:deficiency*; D012873:Skin Diseases, Genetic / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000235:genetics / Q000276:immunology
D048868:Adaptor Proteins, Signal Transducing; C508717:IL17A protein, human; C440021:IL17F protein, human; C448419:IL17RC protein, human; C486701:IL25 protein, human; D020381:Interleukin-17; D018123:Receptors, Interleukin; C414202:TRAF3IP2 protein, human; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins