EBV-induced gene 3 augments IL-23R? protein expression through a chaperone calnexin.

ABSTRACT: 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-? production and failed to induce T cell-dependent colitis in mice. Similarly reduced IFN-? 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-23R?, but not another IL-23R subunit, IL-12R?1, was selectively decreased at the protein level, but not the mRNA level. EBI3 augmented IL-23R? expression via binding to the chaperone molecule calnexin and to IL-23R? in a peptide-dependent manner, but not a glycan-dependent manner. Indeed, EBI3 failed to augment IL-23R? expression in the absence of endogenous calnexin. Moreover, EBI3 poorly augmented the expression of G149R, an IL-23R? 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-23R? protein expression via calnexin under inflammatory conditions.

SUBMITTER: Mizoguchi I 

PROVIDER: S-EPMC7598073 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature