miR-150 Regulates Memory CD8 T Cell Differentiation via c-Myb
Zeyu Chen,
Erietta Stelekati,
Makoto Kurachi,
Sixiang Yu,
Zhangying Cai,
Sasikanth Manne,
Omar Khan,
Xiaolu Yang,
E. John Wherry
Affiliations
Zeyu Chen
Department of Microbiology, University of Pennsylvania, Philadelphia, PA, USA
Erietta Stelekati
Department of Microbiology, University of Pennsylvania, Philadelphia, PA, USA
Makoto Kurachi
Department of Microbiology, University of Pennsylvania, Philadelphia, PA, USA
Sixiang Yu
Department of Cancer Biology and Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
Zhangying Cai
Department of Microbiology, University of Pennsylvania, Philadelphia, PA, USA
Sasikanth Manne
Department of Microbiology, University of Pennsylvania, Philadelphia, PA, USA
Omar Khan
Department of Microbiology, University of Pennsylvania, Philadelphia, PA, USA
Xiaolu Yang
Department of Cancer Biology and Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
E. John Wherry
Department of Microbiology, University of Pennsylvania, Philadelphia, PA, USA
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.
