2. Academic Validation
  3. SZB120 Exhibits Immunomodulatory Effects by Targeting eIF2α to Suppress Th17 Cell Differentiation

SZB120 Exhibits Immunomodulatory Effects by Targeting eIF2α to Suppress Th17 Cell Differentiation

  • J Immunol. 2021 Mar 1;206(5):953-962. doi: 10.4049/jimmunol.2000036.
Linjiao Chen 1 2,  Jing Bai 2,  Danhong Peng 1 2,  Yuanyuan Gao 2,  Xiaojie Cai 2,  Junxun Zhang 2,  Sibei Tang 2,  Liman Niu 2,  Yang Sun 2 3,  Fangzhou Lou 2,  Hong Zhou 2 3,  Qianqian Yin 2,  Zhikai Wang 2,  Libo Sun 2,  Xuemei Du 4,  Zhenyao Xu 2 3,  Hong Wang 2,  Qun Li 5,  Honglin Wang 6 3
Affiliations

Affiliations

  • 1 Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
  • 2 Department of Immunology and Microbiology, Key Laboratory of Cell Differentiation and Apoptosis, Shanghai Institute of Immunology, Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
  • 3 Institute of Translational Medicine, Shanghai Institute of Immunology Center for Microbiota and Immune Related Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
  • 4 State Key Laboratory of Translational Medicine and Innovative Drug Development, Jiangsu Simcere Pharmaceutical Co., Ltd., Nanjing 210042, China; and.
  • 5 Department of Cardiovascular Medicine, State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Institute of Hypertension, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China [email protected] [email protected].
  • 6 Department of Immunology and Microbiology, Key Laboratory of Cell Differentiation and Apoptosis, Shanghai Institute of Immunology, Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; [email protected] [email protected].
PMID: 33483349 DOI: 10.4049/jimmunol.2000036
Abstract

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.

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