Natural Compound 2,2',4'-Trihydroxychalcone Suppresses T Helper 17 Cell Differentiation and Disease Progression by Inhibiting Retinoid-Related Orphan Receptor Gamma T.
Natural Compound 2,2',4'-Trihydroxychalcone Suppresses T Helper 17 Cell Differentiation and Disease Progression by Inhibiting Retinoid-Related Orphan Receptor Gamma T.
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DOI：
10.3390/ijms232314547
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发表时间：
2022-11-22
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
类维生素A相关孤儿受体γt（RORγt）是促炎性Th17细胞分化的重要转录因子，对于Th17细胞介导的炎症反应和病理过程至关重要。核受体 RORγt 的药理学抑制为治疗 Th17 驱动的自身免疫性疾病和器官移植排斥提供了新型免疫调节剂。在这里，我们鉴定了2,2',4'-三羟基查耳酮（TDC），一种天然查耳酮衍生物，直接与RORγt的配体结合域（LBD）结合并抑制其转录激活活性。使用三种Th17相关疾病的小鼠模型，发现给予TDC可有效缓解实验性自身免疫性脑脊髓炎（EAE）、实验性结肠炎和皮肤同种异体移植排斥的疾病发展。总的来说，这些结果表明 TDC 靶向 RORγt 抑制 Th17 细胞极化及其活性，从而表明该化合物在治疗 Th17 相关自身免疫性疾病和器官移植排斥性疾病方面的潜力。
Retinoid-related orphan receptor γt (RORγt), a vital transcription factor for the differentiation of the pro-inflammatory Th17 cells, is essential to the inflammatory response and pathological process mediated by Th17 cells. Pharmacological inhibition of the nuclear receptor RORγt provides novel immunomodulators for treating Th17-driven autoimmune diseases and organ transplant rejection. Here, we identified 2,2′,4′-trihydroxychalcone (TDC), a natural chalcone derivant, binds directly to the ligand binding domain (LBD) of RORγt and inhibited its transcriptional activation activity. Using three mice models of Th17-related diseases, it was found that the administration of TDC effectively alleviated the disease development of experimental autoimmune encephalomyelitis (EAE), experimental colitis, and skin allograft rejection. Collectively, these results demonstrated TDC targeting RORγt to suppress Th17 cell polarization, as well as its activity, thus, indicating the potential of this compound in treating of Th17-related autoimmune disorders and organ transplant rejection disorders.
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影响因子：
30.5
作者：
Manel, Nicolas;Unutmaz, Derya;Littman, Dan R.
通讯作者：
Littman, Dan R.
影响因子：
5.6
作者：
Salehi B;Quispe C;Chamkhi I;El Omari N;Balahbib A;Sharifi-Rad J;Bouyahya A;Akram M;Iqbal M;Docea AO;Caruntu C;Leyva-Gómez G;Dey A;Martorell M;Calina D;López V;Les F
通讯作者：
Les F
影响因子：
4.6
作者：
Murano, M;Maemura, K;Katsu, K
通讯作者：
Katsu, K
影响因子：
7.3
作者：
Martínez-Blanco M;Lozano-Ojalvo D;Pérez-Rodríguez L;Benedé S;Molina E;López-Fandiño R
通讯作者：
López-Fandiño R
影响因子：
4.4
作者：
Rostami, Abdolmohamad;Ciric, Bogoljub
通讯作者：
Ciric, Bogoljub