Inherited IL-17RC deficiency in patients with chronic mucocutaneous candidiasis

J Exp Med. 2015 May 4;212(5):619-31. doi: 10.1084/jem.20141065.

Yun Ling ¹, Sophie Cypowyj ², Caner Aytekin ³, Miguel Galicchio ⁴, Yildiz Camcioglu ⁵, Serdar Nepesov ⁵, Aydan Ikinciogullari ⁶, Figen Dogu ⁶, Aziz Belkadi ¹, Romain Levy ¹, Mélanie Migaud ¹, Bertrand Boisson ², Alexandre Bolze ², Yuval Itan ², Nicolas Goudin ⁷, Julien Cottineau ¹, Capucine Picard ⁸, Laurent Abel ⁹, Jacinta Bustamante ⁸, Jean-Laurent Casanova ¹⁰, Anne Puel ¹¹

Affiliations

1 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.
2 St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065.
3 Department of Pediatric Immunology, Dr. Sami Ulus Maternity and Children's Health and Diseases Training and Research Hospital, 06080 Ankara, Turkey.
4 Victor J. Vilela Children's Hospital, Rosario, 2000 Santa Fe, Argentina.
5 Division of Infectious Diseases, Clinical Immunology, and Allergy, Department of Pediatrics, Cerrahpaşa Medical Faculty, Istanbul University, 34452 Istanbul, Turkey.
6 Department of Pediatric Immunology and Allergy, Ankara University School of Medicine, 06100 Ankara, Turkey.
7 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.
8 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.
9 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.
10 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.
11 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.

PMID: 25918342 DOI: 10.1084/jem.20141065

Abstract

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.

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