| Autor: |
Hill, Elaine V., Ng, T H, Burton, Bronwen R., Oakley, Charly M., Malik, Karim, Wraith, David C. |
| Jazyk: |
angličtina |
| Rok vydání: |
2015 |
| Předmět: |
|
| Zdroj: |
Hill, E V, Ng, T H, Burton, B R, Oakley, C M, Malik, K & Wraith, D C 2015, ' Glycogen synthase kinase-3 controls IL-10 expression in CD4 + effector T-cell subsets through epigenetic modification of the IL-10 promoter ', European Journal of Immunology, vol. 45, no. 4, pp. 1103-1115 . https://doi.org/10.1002/eji.201444661 |
| Popis: |
The serine/threonine kinase glycogen synthase kinase-3 (GSK3) plays an important role in balancing pro- and anti-inflammatory cytokines. We have examined the role of GSK3 in production of IL-10 by subsets of CD4+ T helper cells. Treatment of naive murine CD4+ T cells with GSK3 inhibitors did not affect their production of IL-10. However, treatment of Th1 and Th2 cells with GSK3 inhibitors dramatically increased production of IL-10. GSK3 inhibition also led to upregulation of IL-10 among Th1, Th2, and Th17 subsets isolated from human blood. The encephalitogenic potential of GSK3 inhibitor treated murine Th1 cells was significantly reduced in adoptive transfer experiments by an IL-10-dependent mechanism. Analysis of the murine IL-10 promoter in response to inhibition of GSK3 in Th1 cells showed modification to a transcriptionally active state indicated by changes in histone H3 acetylation and methylation. Additionally, GSK3 inhibition increased expression of the transcription factors c-Maf, Nfil3, and GATA3, correlating with the increase in IL-10. These findings are important in the context of autoimmune disease since they show that it is possible to reprogram disease-causing cells through GSK3 inhibition. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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