Expression data from WT and Aire deficient mTECs

Aire is an important transcription regulator that mediates a role in central tolerance via promoting the promiscuous expression of tissue-specific antigens in the thymus. Although several mouse models of Aire-deficiency have been described, none has analysed the phenotype induced by a mutation that emulates the common 13bp deletion in human APECED by disrupting the first PHD domain in exon 8. Aire-deficient mice with a corresponding mutation showed some disturbance of the medullary epithelial compartment, but at the phenotypic level their T cell compartment appeared relatively normal in the thymus and periphery. An increase in the number of activated T cells was evident, and autoantibodies against several organs were detected. At the histological level, lymphocytic infiltration of several organs indicated the development of autoimmunity, though symptoms were mild and quality of life for Aire-deficient mice appeared equivalent to wild-type littermates, with the exception of male infertility. Vbeta and CDR3 length analysis suggested that each Aire-deficient mouse developed it own polyclonal autoimmune repertoire. Finally, given the prevalence of candidiasis in APECED patients, we examined the control of infection with Candida albicans in Aire-deficient mice. No increase in disease susceptibility was found for either oral or systematic infection. These observations support the view that additional genetic and/or environmental factors contribute substantially to the overt nature of autoimmunity associated with Aire mutations, even for mutations identical to those found in humans with APECED. Keywords: Gene expression comparison between genotypes In this experiment there are 5 samples altogether which consist of two biological replicates of Aire knock-out mTECs and 3 biological replicates of wild type mTECs.自身免疫调节因子（AIRE）是一类关键的转录调控因子，可通过促进胸腺内组织特异性抗原的异位表达，介导中枢免疫耐受过程。尽管此前已有多种AIRE缺陷小鼠模型被报道，但尚无研究针对模拟人类自身免疫性多内分泌腺病伴念珠菌病（APECED）常见13bp缺失突变的模型开展表型分析——该突变通过破坏第8外显子的首个PHD结构域（PHD domain）实现。携带该对应突变的AIRE缺陷小鼠，其髓质上皮细胞组分出现一定程度的紊乱，但在表型层面，胸腺与外周淋巴组织中的T细胞库整体相对正常。不过活化T细胞的数量显著增加，且可检测到针对多种器官的自身抗体。组织学层面可见多器官淋巴细胞浸润，提示自身免疫的发生；尽管症状较为轻微，且除雄性不育外，AIRE缺陷小鼠的生存质量与野生型同窝仔鼠无显著差异。Vβ链（Vβ）与互补决定区3（CDR3）长度分析显示，每只AIRE缺陷小鼠均形成了专属的多克隆自身免疫库。此外，鉴于APECED患者常伴发念珠菌病，我们检测了AIRE缺陷小鼠对白色念珠菌（Candida albicans）感染的防控能力。无论是口腔感染还是系统性感染，小鼠的疾病易感性均未出现升高。上述结果支持这一观点：即便突变与APECED患者的致病变异完全一致，额外的遗传和/或环境因素仍对AIRE突变相关自身免疫的显性表现具有显著的促进作用。 关键词：不同基因型间的基因表达比较 本实验共包含5个样本，其中包括2份AIRE敲除的胸腺髓质上皮细胞（mTECs）生物学重复样本，以及3份野生型mTECs生物学重复样本。