miR-150 Regulates Memory CD8 T Cell Differentiation via c-Myb

• Published in: Cell reports (Cambridge) Vol. 20; no. 11; pp. 2584 - 2597
• Main Authors: Chen, Zeyu, Stelekati, Erietta, Kurachi, Makoto, Yu, Sixiang, Cai, Zhangying, Manne, Sasikanth, Khan, Omar, Yang, Xiaolu, Wherry, E. John
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 12.09.2017; Elsevier
• Subjects: Animals; Apoptosis - genetics; Bcl-2; Bcl-xl; c-Myb; CD8 T cell; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - metabolism; Cell Differentiation; Female; immune memory; Immunity; Immunologic Memory; Male; Mice, Inbred C57BL; Mice, Knockout; MicroRNAs - genetics; MicroRNAs - metabolism; miR-150; Proto-Oncogene Proteins c-myb - metabolism; T cell differentiation; T cell memory; viral infection; Bcl-2; Bcl-xl; viral infection; CD8 T cell; c-Myb; immune memory; T cell memory; T cell differentiation; miR-150
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2017.08.060

MicroRNAs play an important role in T cell responses. However, how microRNAs regulate CD8 T cell memory remains poorly defined. Here, we found that miR-150 negatively regulates CD8 T cell memory in vivo. Genetic deletion of miR-150 disrupted the balance between memory precursor and terminal effector CD8 T cells following acute viral infection. Moreover, miR-150-deficient memory CD8 T cells were more protective upon rechallenge. A key circuit whereby miR-150 repressed memory CD8 T cell development through the transcription factor c-Myb was identified. Without miR-150, c-Myb was upregulated and anti-apoptotic targets of c-Myb, such as Bcl-2 and Bcl-xL, were also increased, suggesting a miR-150-c-Myb survival circuit during memory CD8 T cell development. Indeed, overexpression of non-repressible c-Myb rescued the memory CD8 T cell defects caused by overexpression of miR-150. Overall, these results identify a key role for miR-150 in memory CD8 T cells through a c-Myb-controlled enhanced survival circuit. [Display omitted] •MiR-150 negatively regulates CD8 T cell memory formation•Absence of miR-150 enhances memory CD8 T cell secondary responses•MiR-150 targets c-Myb in CD8 T cells•C-Myb-Bcl-2/Bcl-xl axis positively regulates CD8 T cell memory formation Memory CD8 T cells are critical for long-term adaptive immune protection. In this study, Chen et al. find that miR-150 negatively regulates CD8 T cell memory formation by targeting the c-Myb-Bcl-2/Bcl-xl survival axis.