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

• Published in: Immunology Vol. 152; no. 4; p. 638
• Main Authors: Liu, Zhihao, Wu, Lisha, Zhu, Jing, Zhu, Xiaotong, Zhu, Jianmin, Liu, Jin-Qing, Zhang, Jianchao, Davis, Jonathan P, Varikuti, Sanjay, Satoskar, Abhay R, Zhou, Jie, Li, Ming-Song, Bai, Xue-Feng
• Format: Journal Article
• Language: English
• Published: Oxford Wiley Subscription Services, Inc 01.12.2017
• Subjects: Antigens; Biomarkers; CD44 antigen; Cell surface; Cytokines; Effector cells; Expression vectors; Glycoproteins; Immunological memory; Interleukin 12; Interleukin 27; L-selectin; Lymphocytes; Lymphocytes T; Memory cells; Oct-4 protein; Signaling; Stem cell transplantation; Stem cells
• DOI: 10.1111/imm.12805
• ISSN: 0019-2805

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-27R[alpha]) 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.