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

Yun Ling1, Sophie Cypowyj2, Caner Aytekin3

  • 1Laboratory 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.

The Journal of Experimental Medicine
|April 29, 2015
PubMed

Insights

Interleukin-17 receptor C (IL-17RC) deficiency causes chronic mucocutaneous candidiasis by impairing Candida albicans immunity. This genetic defect highlights IL-17RC

Area of Science:

  • Immunology
  • Genetics
  • Dermatology

Background:

  • Chronic mucocDermatologyosis (CMC) involves recurrent Candida infections affecting skin, nails, and mucosa.
  • Previous studies identified genetic links to IL-17RA, ACT1, and IL-17F deficiencies in CMC.
  • These deficiencies were previously reported in single families.

Purpose of the Study:

  • To investigate the role of IL-17RC in isolated CMC.
  • To characterize the genetic basis and cellular response in patients with IL-17RC deficiency.

Main Methods:

  • Genetic analysis of three unrelated patients with isolated CMC.
  • Assessment of cellular responses to IL-17A, IL-17F, and IL-17E.
  • Evaluation of IL-17RC expression on cell surfaces.

Main Results:

  • Three patients presented with autosomal-recessive IL-17RC deficiency due to homozygous nonsense alleles.
  • Patients exhibited complete absence of IL-17RC expression and cellular response to IL-17A/IL-17F.
  • Crucially, IL-17E (IL-25) response remained intact in these patients.

Conclusions:

  • Human IL-17RC is crucial for mucocutaneous immunity against Candida albicans.
  • IL-17RC deficiency leads to isolated CMC, indicating its specific role in this context.
  • The maintained IL-17E response suggests IL-17RC's function is specific and not universally redundant in IL-17 signaling.

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