PT  - JOURNAL ARTICLE
AU  - Chen, Linjiao
AU  - Bai, Jing
AU  - Peng, Danhong
AU  - Gao, Yuanyuan
AU  - Cai, Xiaojie
AU  - Zhang, Junxun
AU  - Tang, Sibei
AU  - Niu, Liman
AU  - Sun, Yang
AU  - Lou, Fangzhou
AU  - Zhou, Hong
AU  - Yin, Qianqian
AU  - Wang, Zhikai
AU  - Sun, Libo
AU  - Du, Xuemei
AU  - Xu, Zhenyao
AU  - Wang, Hong
AU  - Li, Qun
AU  - Wang, Honglin
TI  - SZB120 Exhibits Immunomodulatory Effects by Targeting eIF2α to Suppress Th17 Cell Differentiation
AID  - 10.4049/jimmunol.2000036
DP  - 2021 Jan 22
TA  - The Journal of Immunology
PG  - ji2000036
4099  - http://www.jimmunol.org/content/early/2021/01/21/jimmunol.2000036.short
4100  - http://www.jimmunol.org/content/early/2021/01/21/jimmunol.2000036.full
AB  - SZB120 inhibits Th17 cell differentiation by enhancing eIF2α phosphorylation.SZB120 efficiently alleviates autoimmune diseases involving the CNS and skin.IL-17–secreting Th17 cells play an important role in the pathogenesis of various inflammatory and autoimmune diseases. IL-17–targeted biologics and small molecules are becoming promising treatments for these diseases. In this study, we report that SZB120, a derivative of the natural compound 3-acetyl-β-boswellic acid, inhibits murine Th17 cell differentiation by interacting with the α-subunit of eukaryotic initiation factor 2 (eIF2α). We showed that SZB120 directly interacts with eIF2α and contributes to serine 51 phosphorylation of eIF2α. The suppressive effect of SZB120 on Th17 cell differentiation was reversed by GSK2606414, an inhibitor of eIF2α phosphokinase. Phosphorylation of eIF2α induced by SZB120 decreased the protein expression of IκBζ, which is important for Th17 cell differentiation. Notably, interaction with eIF2α by SZB120 also impaired glucose uptake and glycolysis in T cells. In vivo, SZB120 treatment of C57BL/6 mice significantly attenuated IL-17/Th17–mediated autoimmune disease. Our study indicates that SZB120 is a promising drug candidate for IL-17/Th17–mediated inflammatory diseases.