慢性黏膜皮肤念珠菌病患者的遗传性白细胞介素-17受体C缺陷

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

作者信息

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

机构信息

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.

出版信息

J Exp Med. 2015 May 4;212(5):619-31. doi: 10.1084/jem.20141065. Epub 2015 Apr 27.

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.

慢性黏膜皮肤念珠菌病（CMC）的特征是皮肤、指甲、口腔和生殖器黏膜反复或持续感染念珠菌属，主要是白色念珠菌。常染色体隐性（AR）白细胞介素17受体A（IL-17RA）和衔接蛋白1（ACT1）缺陷以及常染色体显性白细胞介素17F（IL-17F）缺陷（每个缺陷均在一个家系中报道）是原本健康的患者发生CMC的病因。我们报告了3例来自非亲缘家系的患者，年龄分别为8岁、12岁和37岁，患有孤立性CMC，他们存在AR白细胞介素17受体C（IL-17RC）缺陷。这些患者对于不同的无义等位基因是纯合的，这些等位基因可阻止IL-17RC在细胞表面表达。该缺陷是完全性的，消除了细胞对白细胞介素17A和白细胞介素17F同二聚体及异二聚体的反应。然而，与检测的IL-17RA缺陷和ACT1缺陷患者所观察到的情况不同，这些IL-17RC缺陷患者对白细胞介素17E（IL-25）的反应得以保留。这些自然实验表明，人IL-17RC对于黏膜皮肤抗白色念珠菌免疫至关重要，但在其他方面很大程度上是多余的。