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.
Science. 2011 Apr 1;332(6025):65-8. doi: 10.1126/science.1200439. Epub 2011 Feb 24.
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.
慢性黏膜皮肤念珠菌病（CMCD）的特征是无其他感染或自身免疫表现的患者，由白色念珠菌和在较小程度上由金黄色葡萄球菌引起的皮肤、指甲和口腔及生殖器黏膜的反复或持续性感染。我们报告了 CMCD 的两种遗传病因：细胞因子受体白细胞介素-17 受体 A（IL-17RA）的常染色体隐性缺陷和细胞因子白细胞介素-17F（IL-17F）的常染色体显性缺陷。IL-17RA 缺陷是完全的，消除了细胞对 IL-17A 和 IL-17F 同型和异型二聚体的反应。相比之下，IL-17F 缺陷是部分的，具有突变的 IL-17F 包含的同型和异型二聚体显示出受损，但没有被消除的活性。这些自然实验表明，人类白细胞介素-17A 和白细胞介素-17F 对于针对白色念珠菌的黏膜皮肤免疫是必需的，但在其他方面则很大程度上是冗余的。
