Induction of thymic atrophy and loss of thymic output by type-I interferons during chronic viral infection

Démoulins, Thomas; Baron, Marie-Laurence; Gauchat, Dominique; Kettaf, Nadia; Reed, Steven James; Charpentier, Tania; Kalinke, Ulrich; Lamarre, Alain; Ahmed, Rafi; Sékaly, Rafick-Pierre; Sarkar, Surojit; Kalia, Vandana (2022). Induction of thymic atrophy and loss of thymic output by type-I interferons during chronic viral infection. Virology, 567, pp. 77-86. Elsevier 10.1016/j.virol.2021.12.007

Text D_moulins_Induction_of_thymic_atrophy_and_loss_of_thymic_output.pdf - Published Version Restricted to registered users only Available under License Publisher holds Copyright. Download (7MB)

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-α/β 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 IFNαβR 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.

Interest & Impact

Downloads

1 since deposited on 15 Aug 2022
0 in the past 12 months

Citations

5 Citations in Web of Science ®
6 Citations in Scopus

Search

in Google Scholar™

Services

Actions (login required)

Edit item

Actions (login required)

Edit item