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 EBI 3) or its signalling ( IL ‐27R α ) had profound reduction of Sca‐1 expression in naive ( CD 62L +  CD44 − ), memory ( CD 62L +  CD44 + ) and effector ( CD 62L −  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 +   CD 62L +  CD44 − T memory stem cells may explain why IL ‐27 enhances T‐cell memory.