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

详细信息    查看全文

• 作者：Jan C. Dudda¹ ; ⁷ ; Bruno Salaun¹ ; ⁷ ; Yun Ji² ; ⁶ ; ⁷ ; Douglas C. Palmer² ; Gwennaelle C. Monnot¹ ; Estelle Merck¹ ; Caroline Boudousquie¹ ; Daniel T. Utzschneider⁴ ; Thelma M. Escobar³ ; Rachel Perret¹ ; Stefan A. Muljo³ ; Michael Hebeisen¹ ; ⁵ ; Nathalie Rufer¹ ; ⁵ ; Dietmar Zehn⁴ ; Alena Donda¹ ; Nicholas P. Restifo² ; Werner Held¹ ; Luca Gattinoni² ; ⁶ ; ⁷ ; Pedro Romero¹ ; ⁷ ; ^{pedro.romero@unil.ch}
• 刊名：Immunity
• 出版年：2013
• 出版时间：18 April, 2013
• 年：2013
• 卷：38
• 期：4
• 页码：742-753
• 全文大小：1393 K

文摘

| Figures/TablesFigures/Tables | ReferencesReferences

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.