Cryptotanshinone ameliorates the pathogenesis of systemic lupus erythematosus by blocking T cell proliferation
Cryptotanshinone ameliorates the pathogenesis of systemic lupus erythematosus by blocking T cell proliferation
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隐丹参酮通过阻断 T 细胞增殖改善系统性红斑狼疮的发病机制
DOI：
10.1016/j.intimp.2019.105677
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发表时间：
2019-09-01
影响因子：
5.6
通讯作者：
Zhang, Yun
中科院分区：
文献类型：
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作者：
Du, Yu;Du, Lijun;Zhang, Yun
系统性红斑狼疮（SLE）是一种慢性、破坏性的自身免疫性疾病，伴有严重的器官损害。最近，信号转导和转录激活因子3（STAT 3）在小鼠狼疮中的作用已被描述，表明STAT 3信号转导参与SLE的发展。隐丹参酮（CTS）是一种有效的STAT 3抑制剂，但其作为SLE治疗的潜力仍有待探索。为了确定CTS在SLE中的功能，我们用CTS处理MRL/lpr雌性小鼠。首先，我们发现CTS治疗逆转了狼疮倾向MRL/lpr小鼠脾脏中升高的STAT 3信号，伴随着T细胞数量的显著减少，特别是双阴性（DN）T细胞。进一步的研究表明，CTS在体内外均通过抑制STAT 3的活化而抑制T细胞增殖。同时，我们还证明CTS治疗显著减轻了自身免疫反应，包括显著减少皮肤病变，缩小脾脏大小和延长寿命。此外，CTS治疗降低了自身抗体和促炎细胞因子的水平，以及正常的肾脏结构和功能。这些结果表明CTS抑制了STAT 3的磷酸化，从而抑制了DN T细胞的增殖，最终抑制了SLE的自发发展。总之，我们的数据确定CTS作为SLE患者的潜在治疗药物。
Systemic lupus erythematosus (SLE) is a chronic, devastating autoimmune disorder associated with severe organ damage. Recently, the role of Signal Transducer and Activator of Transcription 3 (STAT3) in murine lupus has been described, suggesting the involvement of STAT3 signaling in the development of SLE. Cryptotanshinone (CTS) is an effective inhibitor of STAT3; however its potential as a SLE treatment remains to be explored. To determine the function of CTS in SLE, we treated MRL/lpr female mice with CTS. Firstly, we found CTS treatment reversed the elevated STAT3 signaling of spleens in lupus-prone MRL/lpr mice, accompanying with a dramatically decreased number of T cells, especially double-negative (DN) T cells. Further research showed that CTS inhibited T cell proliferation via suppressing of STAT3 activation in vitro and in vivo. Consistently, we also proved that CTS treatment significantly alleviated autoimmune response including notably diminished skin lesions, reduced spleen size and increased life span. In addition, CTS treatment decreased the levels of autoantibodies and pro-inflammatory cytokines, as well as normalized structure and function of kidneys. All these data suggested that CTS treatment depressed STAT3 phosphorylation, which resulted in blocked DN T cell proliferation and finally attenuated the spontaneous SLE development. Taken together, our data identify CTS as a potential therapeutic drug for SLE patients.