TY - JOUR
T1 - MicroRNA-155 is required for effector cd8+ t cell responses to virus infection and cancer
AU - Dudda, Jan C.
AU - Salaun, Bruno
AU - Ji, Yun
AU - Palmer, Douglas C.
AU - Monnot, Gwennaelle C.
AU - Merck, Estelle
AU - Boudousquie, Caroline
AU - Utzschneider, Daniel T.
AU - Escobar, Thelma M.
AU - Perret, Rachel
AU - Muljo, Stefan A.
AU - Hebeisen, Michael
AU - Rufer, Nathalie
AU - Zehn, Dietmar
AU - Donda, Alena
AU - Restifo, Nicholas P.
AU - Held, Werner
AU - Gattinoni, Luca
AU - Romero, Pedro
N1 - Funding Information:
We thank D. Labes for technical assistance and I. Luescher for providing tetramers. We also thank P. Martiat and B. Badran for critical input. J.C.D. and B.S. were supported in part by a grant from the MEDIC Foundation, R.P. by New Zealand Foundation for Research, Science and Technology, W.H. and C.B. by the Swiss National Science Foundation (SNSF). G.C.M., D.Z., and P.R. were supported in part by a Prodoc and a Sinergia grants from the SNSF. Y.J., D.C.P., N.P.R. and L.G. were supported by the Intramural Research Programs of the US NIH National Cancer Institute, Center for Cancer Research. T.M.E. and S.A.M. were supported by the Intramural Research Program of the NIH National Institute of Allergy and Infectious Diseases.
PY - 2013/4/18
Y1 - 2013/4/18
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84876746489&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2012.12.006
DO - 10.1016/j.immuni.2012.12.006
M3 - Article
C2 - 23601686
AN - SCOPUS:84876746489
SN - 1074-7613
VL - 38
SP - 742
EP - 753
JO - Immunity
JF - Immunity
IS - 4
ER -
