| First Author | Démoulins T | Year | 2022 |
| Journal | Virology | Volume | 567 |
| Pages | 77-86 | PubMed ID | 35032866 |
| Mgi Jnum | J:333858 | Mgi Id | MGI:7442388 |
| Doi | 10.1016/j.virol.2021.12.007 | Citation | Demoulins T, et al. (2022) Induction of thymic atrophy and loss of thymic output by type-I interferons during chronic viral infection. Virology 567:77-86 |
| abstractText | Type-I interferon (IFN-I) signals exert a critical role in disease progression during viral infections. However, the immunomodulatory mechanisms by which IFN-I dictates disease outcomes remain to be fully defined. Here we report that IFN-I signals mediate thymic atrophy in viral infections, with more severe and prolonged loss of thymic output and unique kinetics and subtypes of IFN-alpha/beta expression in chronic infection compared to acute infection. Loss of thymic output was linked to inhibition of early stages of thymopoiesis (DN1-DN2 transition, and DN3 proliferation) and pronounced apoptosis during the late DP stage. Notably, infection-associated thymic defects were largely abrogated upon ablation of IFNalphabetaR and partially mitigated in the absence of CD8 T cells, thus implicating direct as well as indirect effects of IFN-I on thymocytes. These findings provide mechanistic underpinnings for immunotherapeutic strategies targeting IFN-1 signals to manipulate disease outcomes during chronic infections and cancers. |
