IL-23 receptor expression on γδ T cells correlates with their enhancing or suppressive effects on autoreactive T cells in experimental autoimmune uveitis (EAU)

By Dong-chun Liang, Ai-jun Zuo, H. Shao, W. Born, R. O’Brien, H. Kaplan, Deming Sun. 2013

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We have previously reported that, depending on their activation status, mouse γδ T cells can either enhance or inhibit the activity of IL-17+ autoreactive T cells in experimental autoimmune uveitis. In this study, we showed that γδ T cells in naive C57BL/6 (B6) mouse do not express the IL-23R, whereas in immunized mice, it is expressed on >50% of γδ T cells. In vitro studies showed that IL-23R expression on γδ T cells is modulated by their state of activation, as weakly activated γδ T cells expressed the IL-23R, but highly activated γδ T cells did not. Functional studies showed that IL-23R+ γδ T cells had the strongest suppressive effect on IL-17+ autoreactive T cells, and that this effect was inhibited when the IL-23R was blocked by anti–IL-23R Ab or in the presence of excessive amounts of exogenous IL-23. We conclude that the balance between the enhancing and inhibitory effects of γδ T cells is regulated by their level of IL-23R expression. The expression of variable IL-23R levels allows γδ T cells to have different regulatory effects on adaptive immune responses, conceivably as a result of αβ and γδ T cells competing for IL-23.

Subfields: Immunology