A role for Fli-1 in B cell proliferation: implications for SLE pathogenesis.
A role for Fli-1 in B cell proliferation: implications for SLE pathogenesis.
复制标题
FLI-1在B细胞增殖中的作用：对SLE发病机理的影响。
DOI：
10.1016/j.clim.2008.05.010
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发表时间：
2008-10
影响因子：
8.6
通讯作者：
Zhang, Xian K.
中科院分区：
文献类型：
--
作者：
Bradshaw, Sarah;Zheng, W. Jim;Tsoi, Lam C.;Gilkeson, Gary;Zhang, Xian K.
Fli-1 在正常小鼠中的转基因过度表达会导致类似 SLE 的疾病，并且据报道，在受 SLE 影响的人类和小鼠淋巴细胞中表达增加。减少 MRL/lpr 小鼠中的 Fli-1 表达可降低抗体产生、蛋白尿、肾脏病理学和死亡率。与 Fli-1 野生型表达的小鼠相比，我们在此报道，在易患狼疮的小鼠和对照小鼠中，Fli-1 缺陷的幼稚 B 细胞对几种有丝分裂原的增殖反应降低。在 Fli-1 缺陷的幼稚 B 细胞中，有丝分裂原受体（包括 BCR、TLR4 和 TLR9）的表达没有受到显着影响。在 Fli-1 缺陷的 MRL/lpr B 细胞中，IL12a 转录本上调，NFAT 转录本下调。这些结果表明，Fli-1 缺陷会影响 B 细胞对有丝分裂原的增殖反应，与 BCR 和 TLR 表达无关。已知 IL12a 和 NFAT 会影响增殖，因此被确定为这种效应的潜在介质。这可能是 Fli-1 过度表达导致 B 细胞过度活跃和随后 SLE 发病机制的机制。
Transgenic overexpression of Fli-1 in normal mice leads to SLE-like disease and increased expression was reported in SLE-affected human and murine lymphocytes. Reducing Fli-1 expression in MRL/lpr mice decreased antibody production, proteinuria, renal pathology, and mortality. Compared to those with wild-type expression of Fli-1, we report here that proliferative responses of Fli-1-deficient naïve B cells to several mitogens were reduced in lupus-prone and control mice. Expression of mitogen receptors, including BCR, TLR4, and TLR9, was not significantly impacted in Fli-1-deficient naïve B cells. IL12a transcripts were upregulated and NFAT transcripts were downregulated in Fli-1-deficient MRL/lpr B cells. These results demonstrate that Fli-1 deficiency affects B cell proliferative responses to mitogens, independent of BCR and TLR expression. IL12a and NFAT, known to influence proliferation, were identified as potential mediators of this effect. This may be a mechanism by which overexpression of Fli-1 contributes to B cell hyperactivity and subsequent SLE pathogenesis.
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影响因子：
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