IRF-4 is associated with the development of granulomas in autoimmune disease

自身免疫性疾病中肉芽肿形成的机制尚不清楚。我们发现转录因子irf4缺陷的狼疮易感性MRL/lpr小鼠在包括肺在内的多个器官中发生朗汉斯巨细胞肉芽肿。我们还发现，irf4缺陷的MRL/lpr小鼠产生IFN-g的Th1细胞数量增加，血清IFN-g水平升高。而转录因子irf1缺失的MRL/lpr小鼠肺中产生il -4的Th2细胞和含有异物巨细胞的肉芽肿数量增加。我们的数据表明，转录因子IRF4和IRF1在维持Th1/ th2细胞/细胞因子平衡中发挥重要作用，这些转录因子的缺陷导致多器官肉芽肿病变的发展。

Mechanisms of granuloma formation in autoimmune diseases is unknown. We found that transcription factor IRF4-deficient lupus-prone MRL/lpr mice develop granulomas with Langhans giant cells in multiple organs including lung. We also found that IRF4-deficient MRL/lpr mice had increased numbers of IFN-g-producing Th1 cells with elevated levels of serum IFN-g. While, transcription factor IRF1-deficient MRL/lpr mice had increased numbers of IL-4-producing Th2 cells and granulomas with foreign body giant cells in their lung. Our data indicate that transcription factor IRF4 and IRF1 play important roles to maintain Th1/Th2-cell/cytokine balance, and defect of these transcription factors causes development of granulomatous lesions in multiple organs.