Immunity
Volume 38, Issue 4, 18 April 2013, Pages 742-753
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Article
MicroRNA-155 Is Required for Effector CD8+ T Cell Responses to Virus Infection and Cancer

https://doi.org/10.1016/j.immuni.2012.12.006Get rights and content
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Summary

MicroRNAs (miRNAs) regulate the function of several immune cells, but their role in promoting CD8+ T cell immunity remains unknown. Here we report that miRNA-155 is required for CD8+ T cell responses to both virus and cancer. In the absence of miRNA-155, accumulation of effector CD8+ T cells was severely reduced during acute and chronic viral infections and control of virus replication was impaired. Similarly, Mir155−/− CD8+ T cells were ineffective at controlling tumor growth, whereas miRNA-155 overexpression enhanced the antitumor response. miRNA-155 deficiency resulted in accumulation of suppressor of cytokine signaling-1 (SOCS-1) causing defective cytokine signaling through STAT5. Consistently, enforced expression of SOCS-1 in CD8+ T cells phenocopied the miRNA-155 deficiency, whereas SOCS-1 silencing augmented tumor destruction. These findings identify miRNA-155 and its target SOCS-1 as key regulators of effector CD8+ T cells that can be modulated to potentiate immunotherapies for infectious diseases and cancer.

Highlights

► TCR affinity regulates miRNA-155 expression crucial for CD8+ T cell accumulation. ► CD8 T cell survival and virus control in chronic infection depend on miRNA-155. ► miRNA-155 enhances CD8+ T cell cytokine signaling via targeting of SOCS-1. ► miRNA-155 and SOCS-1 modulation in specific CD8 T cells enhance their tumor control

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Present address: Experimental Transplantation and Immunology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA

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These authors contributed equally to this work