Immunotherapeutic analysis using newly established murine models for Sjogren' s syndrome

我们报道了RbAp48和CCR7基因敲除(KO)小鼠的转基因(TG)表达导致了类似干燥S综合征的自身免疫性外分泌病的发生。随着年龄的增长，CD4~+T细胞介导的自身免疫损伤加重，并与自身抗体的产生有关。我们发现唾液上皮细胞可以产生干扰素-γ和白介素18，从而激活干扰素调节因子-1和第二类反式激活因子。CCR7KO小鼠的调节性T(Treg)细胞明显滞留在淋巴结内，不能在外分泌器官内巡逻以保护自身免疫。靶向RbAp48基因并应用体内siRNA给药可预防自身免疫性损伤。这些结果表明上皮细胞的一种新的免疫活性作用，导致在发展基于性别的自身免疫之前失去局部耐受性。

We reported that transgenic(TG) expression of RbAp48, and CCR7 knockout(KO) mice resulted in the development of autoimmune exocrinopathy resembling Sjogren' s syndrome. CD4^+ T cell-mediated autoimmune lesions were aggravated with age, in association with autoantibody productions. We obtained evidences that salivary epithelial cells can produce interferon-γand interleukin-18, which activates interferon regulatory factor-1(IRF-1), and class II transactivator(CIITA). Regulatory T(Treg) cells were significantly retained in the lymph nodes of CCR7KO mice, and failed to patrol within the exocrine organs to protect autoimmunity. The gene targeting for RbAp48 with application of in vivo siRNA administration prevented autoimmune lesions. These results indicate a novel immunocompetent role of epithelial cells, resulting in loss of local tolerance prior to developing gender-based autoimmunity.