Table_1_The IL-20RB receptor and the IL-20 signaling pathway in regulating host defense in oral mucosal candidiasis.docx

Pseudomembranous candidiasis (thrush), erythematous candidiasis, and fungal esophagitis are infections of the barrier mucosa of the upper gastrointestinal tract. The majority of these infections are caused by Candida albicans, an opportunistic fungal pathogen that frequently exists as a harmless commensal on mucosal surfaces lining the gastrointestinal tract. Oral infections are initiated in the superficial stratified squamous epithelium, in which keratinocytes are the most abundant host cells and are the initial points of contact with C. albicans present in saliva. Intrinsic features of oral keratinocytes are likely to play important roles in host defense and tissue homeostasis in oral candidiasis. One understudied pathway that may be important for modulating oral candidiasis is the IL-20 cytokine signaling pathway that employs keratinocyte IL-20RB receptors as ligands for IL-19, IL-20, and IL-24. We report that production of human oral keratinocyte il24 mRNA and protein are stimulated during co-culture with C. albicans. To test the role of the IL-20 family signaling pathway in oral candidiasis, Il20rb-/- mice (lacking the IL-20RB receptor) were compared to wild-type mice in a murine model of oropharyngeal candidiasis. Fungal burdens and percent loss in body weight were determined. Despite comparable fungal burdens, the Il20rb-/- mice exhibited less weight loss over the course of their infection compared to the B6 mice, suggestive of reduced overall disease consequences in the mutant mice. Interference with IL-20 family cytokine signaling may be useful for augmenting the ability of the host to defend itself against pathogens.

假膜型念珠菌病（thrush，鹅口疮）、红斑型念珠菌病及真菌性食管炎均为上消化道屏障黏膜感染性疾病。这类感染多由白念珠菌（Candida albicans）引起——白念珠菌是一种机会性真菌病原体，通常可作为无害共生菌定植于消化道黏膜表面。口腔感染始发于浅表复层鳞状上皮，其中角质形成细胞（keratinocytes）是数量最多的宿主细胞，也是与唾液中白念珠菌初始接触的位点。口腔角质形成细胞的内在特征可能在口腔念珠菌病的宿主防御与组织稳态中发挥重要作用。尚未被充分研究的IL-20细胞因子信号通路，或可调控口腔念珠菌病；该通路以角质形成细胞表面的IL-20RB受体作为结合靶点，配体为IL-19、IL-20及IL-24。本研究发现，在与白念珠菌共培养时，人口腔角质形成细胞的IL-24（il24）信使核糖核酸（mRNA）及蛋白的表达会被激活上调。为验证IL-20家族信号通路在口腔念珠菌病中的作用，本研究通过口咽念珠菌病小鼠模型，将IL-20RB受体敲除（Il20rb-/-）小鼠与野生型B6小鼠进行对比，检测两组小鼠的真菌负荷与体重下降百分比。尽管两组的真菌负荷无显著差异，但IL-20RB敲除小鼠在感染过程中的体重下降程度显著低于野生型B6小鼠，提示该基因敲除小鼠的整体疾病症状有所减轻。由此可见，靶向干扰IL-20家族细胞因子信号通路或可增强宿主抵御病原体的能力。