期刊
BLOOD
卷 118, 期 20, 页码 5487-5497出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2011-05-355644
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资金
- pathway to independence grant
- National Cancer Institute
- California Institute for Regenerative Medicine
- American Cancer Society [RSG-10-157-01-LIB]
- American Diabetes Association [1-10-JF-28]
- National Institute of Allergy and Infectious Diseases [R56AI091878]
Mir-17-92 encodes 6 miRNAs inside a single polycistronic transcript, the proper expression of which is critical for early B-cell development and lymphocyte homeostasis. However, during the T-cell antigen response, the physiologic function of endogenous miR-17-92 and the roles of the individual miRNAs remain elusive. In the present study, we functionally dissected the miR-17-92 cluster and revealed that miR-17 and miR-19b are the key players controlling Th1 responses through multiple coordinated biologic processes. These include: promoting proliferation, protecting cells from activation-induced cell death, supporting IFN-gamma production, and suppressing inducible regulatory T-cell differentiation. Mechanistically, we identified Pten (iphosphatase and tensin homolog) as the functionally important target of miR-19b, whereas the function of miR-17 is mediated by TGF beta RII and the novel target CREB1. Because of its vigorous control over the Th1 cell-inducible regulatory T cell balance, the loss of miR-17-92 in CD4 T cells results in tumor evasion. Our results suggest that miR-19b and miR-17 could be harnessed to enhance the efficacy of T cell-based tumor therapy. (Blood. 2011;118(20):5487-5497)
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