MicroRNA-155 Is Required for Effector CD8(+) T Cell Responses to Virus Infection and Cancer.

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2013

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info:eu-repo/semantics/altIdentifier/doi/10.1016/j.immuni.2012.12.006

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info:eu-repo/semantics/altIdentifier/pmid/23601686

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info:eu-repo/semantics/altIdentifier/eissn/1097-4180

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info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_C465F0F1D8F88

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J.C. Dudda et al., « MicroRNA-155 Is Required for Effector CD8(+) T Cell Responses to Virus Infection and Cancer. », Serveur académique Lausannois, ID : 10.1016/j.immuni.2012.12.006


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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.

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