Lithocholic acid inhibits dendritic cell activation by reducing intracellular glutathione via TGR5 signaling.
Lithocholic acid inhibits dendritic cell activation by reducing intracellular glutathione via TGR5 signaling.
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石胆酸通过 TGR5 信号传导减少细胞内谷胱甘肽来抑制树突状细胞活化
DOI：
10.7150/ijbs.71287
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发表时间：
2022
影响因子：
9.2
通讯作者：
Li, Hong
中科院分区：
文献类型：
--
作者：
Hu, Jianping;Zhang, Yiting;Yi, Shenglan;Wang, Chaokui;Huang, Xinyue;Pan, Su;Yang, Jinglu;Yuan, Gangxiang;Tan, Sisi;Li, Hong
树突状细胞（Dendritic cells，DCs）是主要的抗原提呈细胞，在自身免疫性葡萄膜炎中起重要作用。新出现的证据表明胆汁酸（BA）调节DC成熟。然而，BAs调节DCs功能的潜在机制仍需澄清。在这里，我们证明，石胆酸（LCA）抑制骨髓来源的树突状细胞（BMDCs）的促炎细胞因子的产生和表面分子的表达。LCA通过调节脾脏CD 11 C +MHCIIhigh DC的成熟来减轻EAU的严重程度。值得注意的是，Takeda G蛋白偶联受体5（TGR 5）缺陷部分逆转了LCA对体外和体内DC的抑制作用。TGR 5激活还通过抑制DC中谷胱甘肽的产生和诱导氧化应激来下调NF-κB和MAPK途径，从而导致DC中的细胞凋亡和自噬。此外，LCA或INT-777治疗增加了活动性BD患者单核细胞衍生树突状细胞（MD-DC）中的TGR 5表达，而LCA和TGR 5激动剂均抑制MD-DC的活化。这些结果表明，LCA和TGR 5激动剂可能是治疗自身免疫性葡萄膜炎的潜在治疗药物。
Dendritic cells (DCs) are the major antigen-presenting cells and play an important role in autoimmune uveitis. Emerging evidence suggests that bile acids (BAs) regulate DCs maturation. However, the underlying mechanisms by which BAs regulate the function of DCs still need to be clarified. Here, we demonstrate that lithocholic acid (LCA) inhibits the production of pro-inflammatory cytokines and the expression of surface molecules in bone marrow-derived dendritic cells (BMDCs). LCA attenuates the severity of EAU by modulating the maturation of splenic CD11C+MHCIIhigh DCs. Notably, Takeda G-protein coupled receptor 5 (TGR5) deficiency partially reverses the inhibitory effect of LCA on DCs in vitro and in vivo. TGR5 activation also downregulates the NF-κB and MAPK pathways by inhibiting glutathione production and inducing oxidative stress in DCs, which leads to apoptosis and autophagy in DCs. In addition, LCA or INT-777 treatment increases the TGR5 expression in monocyte-derived dendritic cells (MD-DCs) of patients with active BD, whereas both LCA and TGR5 agonists inhibit the activation of MD-DCs. These results suggest that LCA and TGR5 agonists might be potential therapeutic drugs for the treatment of autoimmune uveitis.
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DOI：
10.1084/jem.20100977
发表时间：
2011-10-24
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Ghoreschi K;Brück J;Kellerer C;Deng C;Peng H;Rothfuss O;Hussain RZ;Gocke AR;Respa A;Glocova I;Valtcheva N;Alexander E;Feil S;Feil R;Schulze-Osthoff K;Rupec RA;Lovett-Racke AE;Dringen R;Racke MK;Röcken M
通讯作者：
Röcken M
影响因子：
3.5
作者：
Bolling, Anette Kocbach;Samuelsen, Jan Tore;Mathisen, Gro Haarklou
通讯作者：
Mathisen, Gro Haarklou
影响因子：
4.4
作者：
Biagioli, Michele;Carino, Adriana;Fiorucci, Stefano
通讯作者：
Fiorucci, Stefano
影响因子：
11.4
作者：
Ghezzi P
通讯作者：
Ghezzi P
影响因子：
7.3
作者：
Fiorucci S;Biagioli M;Zampella A;Distrutti E
通讯作者：
Distrutti E