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SZB120 Exhibits Immunomodulatory Effects by Targeting eIF2α to Suppress Th17 Cell Differentiation
- Source :
- J Immunol
- Publication Year :
- 2021
- Publisher :
- The American Association of Immunologists, 2021.
-
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.
- Subjects :
- Male
Glucose uptake
Cellular differentiation
Eukaryotic Initiation Factor-2
Immunology
Autoimmunity
Autoimmune Diseases
Serine
Pathogenesis
Mice
In vivo
medicine
Animals
Immunologic Factors
Immunology and Allergy
Glycolysis
Phosphorylation
Cells, Cultured
Autoimmune disease
Biological Products
Chemistry
Interleukin-17
Cell Differentiation
medicine.disease
Triterpenes
Cell biology
Mice, Inbred C57BL
Th17 Cells
Female
Subjects
Details
- ISSN :
- 15506606 and 00221767
- Volume :
- 206
- Database :
- OpenAIRE
- Journal :
- The Journal of Immunology
- Accession number :
- edsair.doi.dedup.....555588577fbebf80e70cf0f6c5bb60db