| First Author | Hanieh H | Year | 2018 |
| Journal | Eur J Immunol | Volume | 48 |
| Issue | 4 | Pages | 593-604 |
| PubMed ID | 29244194 | Mgi Jnum | J:261340 |
| Mgi Id | MGI:6151318 | Doi | 10.1002/eji.201747109 |
| Citation | Hanieh H, et al. (2018) Arid5a stabilizes OX40 mRNA in murine CD4(+) T cells by recognizing a stem-loop structure in its 3'UTR. Eur J Immunol 48(4):593-604 |
| abstractText | AT-rich interactive domain-containing protein 5a (Arid5a) is an RNA-binding protein (RBP) required for autoimmunity via stabilization of interleukin-6 (Il6) and signal transducer and activator of transcription 3 (STAT3) mRNAs. However, the roles of Arid5a in Th17 cells and its association with autoimmunity remain unknown. Here, we show that the levels of Arid5a and OX40 are correlated in CD4(+) T cells under Th17 conditions in an IL-6-dependent manner. Lack of Arid5a in T cells reduced OX40 expression levels and repressed IL-17 production in response to OX40 ligation. Arid5a stabilized OX40 mRNA by recognizing the alternative decay element (ADE)-like stem-loop (SL) in the 3'' untranslated region (3''UTR). Interestingly, Arid5a impaired the RNA-destabilizing functions of Regnase-1 and Roquin-1 on OX40 ADE-like SL. In EAE, Arid5a-deficient mice exhibited resistance to EAE, with reduced OX40 expression in CD4(+) T cells, and the number of CD4(+) CD45(+) T cells was decreased in CNS. Furthermore, ameliorated EAE was induced by adoptive transfer of Arid5a(-/-) encephalitogenic CD4(+) T cells expressing less OX40 mRNA and producing less IL-17. In conclusion, our findings indicate that the Arid5a/OX40 axis in CD4(+) T cells may have important implications in pathogenesis of autoimmune diseases such as EAE. |
