| First Author | Volpe E | Year | 2019 |
| Journal | Cell Death Differ | Volume | 26 |
| Issue | 6 | Pages | 1169-1180 |
| PubMed ID | 30258098 | Mgi Jnum | J:297008 |
| Mgi Id | MGI:6468856 | Doi | 10.1038/s41418-018-0201-9 |
| Citation | Volpe E, et al. (2019) The RNA binding protein Sam68 controls T helper 1 differentiation and anti-mycobacterial response through modulation of miR-29. Cell Death Differ 26(6):1169-1180 |
| abstractText | Polarization of naive T cells into interferon (IFN)-gamma-producing T helper 1 (Th1) cells is an essential event in the inflammatory response to pathogens. Herein, we identify the RNA binding protein Sam68 as a specific modulator of Th1 differentiation. Sam68-knockout (ko) naive T cells are strongly defective in IL-12-mediated Th1 polarization and express low levels of T-bet and Eomes. Consequently, Sam68-ko Th1 cells are significantly impaired in IFN-gamma production. Moreover, we found that Sam68 is required for the induction of an inflammatory Th1 response during Mycobacterium bovis Bacillus Calmette-Guerin (BCG) infection, thus limiting bacterial dissemination in the lungs. Mechanistically, Sam68 directly binds to the microRNA miR-29, a negative regulator of Th1 response, and inhibits its expression during BCG infection. These findings uncover a novel post-transcriptional mechanism required for the Th1-mediated defense against intracellular pathogens and identify a new function for Sam68 in the regulation of the immune response. |
