| First Author | Khan AA | Year | 2013 |
| Journal | Blood | Volume | 121 |
| Issue | 22 | Pages | 4473-83 |
| PubMed ID | 23596046 | Mgi Jnum | J:198459 |
| Mgi Id | MGI:5496762 | Doi | 10.1182/blood-2012-06-435412 |
| Citation | Khan AA, et al. (2013) MicroRNA-17~92 regulates effector and memory CD8 T-cell fates by modulating proliferation in response to infections. Blood 121(22):4473-83 |
| abstractText | The precise microRNAs and their target cellular processes involved in generation of durable T-cell immunity remain undefined. Here we show a dynamic regulation of microRNAs as CD8 T cells differentiate from naive to effector and memory states, with short-lived effectors transiently expressing higher levels of oncogenic miR-17-92 compared with the relatively less proliferating memory-fated effectors. Conditional CD8 T-cell-intrinsic gain or loss of expression of miR-17-92 in mature cells after activation resulted in striking reciprocal effects compared with wild-type counterparts in the same infection milieu-miR-17-92 deletion resulted in lesser proliferation of antigen-specific cells during primary expansion while favoring enhanced IL-7Ralpha and Bcl-2 expression and multicytokine polyfunctionality; in contrast, constitutive expression of miR-17-92 promoted terminal effector differentiation, with decreased formation of polyfunctional lymphoid memory cells. Increased proliferation upon miR-17-92 overexpression correlated with decreased expression of tumor suppressor PTEN and increased PI3K-AKT-mTOR signaling. Thus, these studies identify miR17-92 as a critical regulator of CD8 T-cell expansion and effector and memory lineages in the physiological context of acute infection, and present miR-17-92 as a potential target for modulating immunologic outcome after vaccination or immunotherapeutic treatments of cancer, chronic infections, or autoimmune disorders. |
