| First Author | Mizoguchi I | Year | 2020 |
| Journal | J Clin Invest | Volume | 130 |
| Issue | 11 | Pages | 6124-6140 |
| PubMed ID | 32809973 | Mgi Jnum | J:302494 |
| Mgi Id | MGI:6508170 | Doi | 10.1172/JCI122732 |
| Citation | Mizoguchi I, et al. (2020) EBV-induced gene 3 augments IL-23Ralpha protein expression through a chaperone calnexin. J Clin Invest 130(11):6124-6140 |
| abstractText | Epstein-Barr virus-induced gene 3 (EBI3) is a subunit common to IL-27, IL-35, and IL-39. Here, we explore an intracellular role of EBI3 that is independent of its function in cytokines. EBI3-deficient naive CD4+ T cells had reduced IFN-gamma production and failed to induce T cell-dependent colitis in mice. Similarly reduced IFN-gamma production was observed in vitro in EBI3-deficient CD4+ T cells differentiated under pathogenic Th17 polarizing conditions with IL-23. This is because the induction of expression of one of the IL-23 receptor (IL-23R) subunits, IL-23Ralpha, but not another IL-23R subunit, IL-12Rbeta1, was selectively decreased at the protein level, but not the mRNA level. EBI3 augmented IL-23Ralpha expression via binding to the chaperone molecule calnexin and to IL-23Ralpha in a peptide-dependent manner, but not a glycan-dependent manner. Indeed, EBI3 failed to augment IL-23Ralpha expression in the absence of endogenous calnexin. Moreover, EBI3 poorly augmented the expression of G149R, an IL-23Ralpha variant that protects against the development of human colitis, because binding of EBI3 to the variant was reduced. Taken together with the result that EBI3 expression is inducible in T cells, the present results suggest that EBI3 plays a critical role in augmenting IL-23Ralpha protein expression via calnexin under inflammatory conditions. |
