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黄芩苷通过抑制滤泡辅助性 T 细胞(Tfh 细胞)分化和诱导 T 调节细胞(Tfr 细胞)扩增来改善狼疮自身免疫。

Baicalin ameliorates lupus autoimmunity by inhibiting differentiation of Tfh cells and inducing expansion of Tfr cells.

机构信息

Department of Dermatology, Zhongshan Hospital, Fudan University, Shanghai, China.

Division of Rheumatology, Huashan Hospital, Fudan University, Shanghai, China.

出版信息

Cell Death Dis. 2019 Feb 13;10(2):140. doi: 10.1038/s41419-019-1315-9.

Abstract

Baicalin is a natural compound isolated from Chinese herb, which has been reported as an anti-inflammatory drug. Here, we demonstrated that Baicalin treatment could reduce urine protein, inhibit anti-ds-DNA antibody titers, and ameliorate lupus nephritis in MRL/lpr lupus-prone mice. Baicalin inhibited Tfh cell differentiation and IL-21 production, but promoted Foxp3 regulatory T cell differentiation including part of follicular regulatory T (Tfr) cells. Intravenous injection of Baicalin-induced Foxp3 regulatory T cells could relieve nephritis, inhibit Tfh cell differentiation and IL-21 production. Baicalin inhibited mTOR activation, reduced mTOR agonist-mediated Tfh cell expansion and increased Tfr cells. These data suggest that Baicalin attenuates lupus autoimmunity by up- and downregulating the differentiation of Tfr cells and Tfh cells, respectively. Baicalin and ex vivo expanded Foxp3 regulatory T cells are promising therapeutics for the treatment of lupus.

摘要

黄芩素是一种从中国草药中分离出来的天然化合物,已被报道为一种抗炎药物。在这里,我们证明了黄芩素治疗可以减少尿蛋白,抑制抗 ds-DNA 抗体滴度,并改善 MRL/lpr 狼疮易感小鼠的狼疮肾炎。黄芩素抑制 Tfh 细胞分化和 IL-21 产生,但促进 Foxp3 调节性 T 细胞分化,包括部分滤泡调节性 T(Tfr)细胞。黄芩素诱导的 Foxp3 调节性 T 细胞静脉注射可缓解肾炎,抑制 Tfh 细胞分化和 IL-21 产生。黄芩素抑制 mTOR 激活,减少 mTOR 激动剂介导的 Tfh 细胞扩增并增加 Tfr 细胞。这些数据表明,黄芩素通过上调和下调 Tfr 细胞和 Tfh 细胞的分化来减轻狼疮自身免疫。黄芩素和体外扩增的 Foxp3 调节性 T 细胞是治疗狼疮的有前途的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7356/6374440/833eb469b01a/41419_2019_1315_Fig1_HTML.jpg

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