慢性皮肤粘膜念珠菌病（CMC）是一组以慢性反复性皮肤、甲及粘膜的表浅念珠菌感染为特点的临床综合征。近年来对其遗传背景的研究已证实宿主免疫缺陷与其发病存在密切关系。目前CMC最常见的致病基因为STAT1基因功能增强性突变，它导致患者Th17细胞应答缺陷、抑制Th17细胞分化细胞因子产生、STAT1高磷酸化、PIAS1-STAT1 相互作用增强等免疫异常，进而引起对于真菌的易感性。目前治疗CMC仍需终生使用抗真菌药物，亟待开展有针对性的免疫治疗基础研究。申请人前期已证实我国CMC患者存在STAT1基因突变，在本申请中，拟利用患者外周血单个核细胞，围绕STAT1突变的免疫缺陷主要环节，开展G/GM-CSF、细胞因子中和抗体、组蛋白去乙酰化酶抑制剂、甲基供体四种新型免疫治疗方案的体外研究，以期有针对性地纠正患者的免疫缺陷，为今后开展免疫治疗的动物研究和临床研究奠定基础。

Chronic mucocutaneous candidiasis (CMC) is a group of superficial Candida infections involving skin, nail and mucous membrane. It is characterized by its chronic course, early onset and recalcitrant lesions. Recent studies have identified several underlying genetic deficiencies of CMC. Among them, STAT1 is the most common one to cause AD-CMC. STAT1 is activated by tyrosine phosphorylation when interferons bind to their receptors, which plays a pivotal role in the defense against pathogens. Heterozygous missense mutations of STAT1 in AD-CMC were reported to cause deficiency of Th17 responses, increased production of cytokines that inhibit Th17 differentiation, hyperphosphorylation of STAT1 molecules, and enhanced PIAS1/STAT1 interaction, which then predispose patients to mucocutaneous Candida infections. Although the mechanisms of STAT1 gain-of-function mutations have been more and more elucidated, no targeted treatment other then lifelong antifungal therapy exists for CMC patients. In previous studies, we identified STAT1 mutations in Chinese CMC patients. And in this proposed study we will use PBMCs from CMC patients, to explore new targeted immunotherapies based on previous reported immunodeficiency mechanisms. We will investigate the effect of adding G-CSF/GM-CSF, neutralizing anti-cytokine antibodies, HDAC inhibitors and S-adenosylmethionine. Our study aims to determine whether we can restore the molecular and functional defects of CMC, and may serve as potential treatment strategies for CMC in the future.