Interleukin‐27 signalling induces stem cell antigen‐1 expression in T lymphocytes in vivo

Summary Stem cell antigen‐1 (Sca‐1/Ly6A/E) is a cell surface glycoprotein that is often used as a biomarker for stem cells and cell stemness. However, it is not clear what factors can directly induce the expression of Sca‐1/Ly6A/E in T lymphocytes in vivo, and if induction of Sca‐1 is associated with T cell stemness. In this study, we show that interleukin‐27 (IL‐27), a member of the IL‐12 family of cytokines, directly induces Sca‐1 expression in T cells in vivo. We found that mice‐deficient for IL‐27 (either P28 or EBI3) or its signalling (IL‐27Rα) had profound reduction of Sca‐1 expression in naive (CD62L+ CD44−), memory (CD62L+ CD44+) and effector (CD62L− CD44+) T cells. In contrast, in vivo delivery of IL‐27 using adeno‐associated viral vectors strongly induced the expression of Sca‐1 in naive and memory/effector T‐cell populations in an IL‐27 receptor‐ or signal transducer and activator of transcription 1‐dependent manner. Interestingly, IL‐27‐induced Sca‐1+ T cells do not express or up‐regulate classic stem cell‐associated genes such as Nanog, Oct4, Sox2 and Ctnnb1. However, IL‐27‐induced Sca‐1+ T cells had increased expression of effector/memory‐associated transcription factor T‐bet, Eomes and Blimp1. Hence, IL‐27 signalling directly induces the expression of Sca‐1/Ly6A/E expression in T cells. Direct expansion of Sca‐1+ CD62L+ CD44− T memory stem cells may explain why IL‐27 enhances T‐cell memory. Interleukin‐27 signalling induces the expression of stem cell antigen‐1 in mature T lymphocytes in vivo, which leads to the expansion of the T memory stem cell population.