Department of Dermatology, Zhongshan Hospital, Fudan University, Shanghai, China.
Division of Rheumatology, Huashan Hospital, Fudan University, Shanghai, China.
Cell Death Dis. 2019 Feb 13;10(2):140. doi: 10.1038/s41419-019-1315-9.
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.
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。