Interferon-sensitized hematopoietic progenitors dynamically alter organismal immunity.

ABSTRACT: Inflammation has enduring impacts on organismal immunity. However, the precise mechanisms by which tissue-restricted inflammation conditions systemic responses are poorly understood. Here, we leveraged a highly compartmentalized model of skin inflammation and identified a surprising type I interferon (IFN)-mediated activation of hematopoietic stem/progenitor cells (HSPCs) that results in profound changes to systemic host responses. Post-inflamed mice were protected from atherosclerosis and had worse outcomes following influenza virus infection. This IFN-mediated HSPC modulation was dependent on IFNAR signaling and could be recapitulated with the administration of recombinant IFN-α. Importantly, the transfer of post-inflamed HSPCs was sufficient to transmit the immune suppression phenotype.

SUBMITTER: Guillamot M 

PROVIDER: S-EPMC12614298 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature