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Publication : Interleukin-27 signalling induces stem cell antigen-1 expression in T lymphocytes in vivo.

First Author  Liu Z Year  2017
Journal  Immunology Volume  152
Issue  4 Pages  638-647
PubMed ID  28758191 Mgi Jnum  J:248992
Mgi Id  MGI:5920814 Doi  10.1111/imm.12805
Citation  Liu Z, et al. (2017) Interleukin-27 signalling induces stem cell antigen-1 expression in T lymphocytes in vivo. Immunology 152(4):638-647
abstractText  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-27Ralpha) 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.
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