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Interleukin‐27 signalling induces stem cell antigen‐1 expression in T lymphocytes in vivo
Author(s) -
Liu Zhihao,
Wu Lisha,
Zhu Jing,
Zhu Xiaotong,
Zhu Jianmin,
Liu JinQing,
Zhang Jianchao,
Davis Jonathan P.,
Varikuti Sanjay,
Satoskar Abhay R.,
Zhou Jie,
Li MingSong,
Bai XueFeng
Publication year - 2017
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12805
Subject(s) - biology , cd44 , il 2 receptor , stem cell , t cell , microbiology and biotechnology , interleukin 21 , memory t cell , sox2 , homeobox protein nanog , interleukin 3 , cell , immunology , transcription factor , embryonic stem cell , immune system , induced pluripotent stem cell , biochemistry , genetics , gene
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.