Interferon-sensitized hematopoietic progenitors dynamically alter organismal immunity
Year: 2025
Type: article
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. IFN modulation of HSPCs was rooted both in long-term changes in chromatin accessibility and the emergence of an IFN-responsive functional state from multiple progenitor populations. Collectively, our data reveal the profound and enduring effect of transient inflammation and more specifically type I IFN signaling and set the stage for a more nuanced understanding of HSPC functional modulation by peripheral immune signals.
Source: The Journal of Immunology
Authors: Maria Guillamot, Wenceslao Martinez-Navarrete, Jack Major, Ipsita Subudhi, Varvara Paraskevopoulou, Aleksandr Prystupa, Ikjot Sidhu, Anna Yeaton, Filadelfia Tadjibaeva, Maria Laskou, Carmen Hannemann, Casey Donahoe, Destini Wiseman, Riley Hamilton, Iannis Aifantis, Shruti Naik, Ada Weinstock
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Awards: G1602249644, Regulation of emergency hematopoiesis by the ubiquitin-proteasome system, Mechanisms underlying caloric restriction-mediated resolution of atherosclerosis, Decoding microbe-epithelial stem cell interactions in health and disease, Multispectral imaging & analysis of intact tissue sections w/ the Perkin Elmer Vectra, Mechanisms underlying caloric restriction-mediated resolution of atherosclerosis, Regulation of atherosclerosis regression and macrophage polarization by a novel Wnt-STAT3 axis, Mechanisms that retard atherosclerosis regression in insulin resistant and obese mice, G9000096011, G9000157724, G9000294662, G9000328552, G9000339110, The role of inflammation in the regulation of immune response in acute myeloid leukemia, NRSA Training Core, Cancer Center Support Grant, Dissecting innate immune signaling in pre-leukemia evolution, Macrophage Dysfunction in Atherosclerosis and Cardiometabolic Diseases
OpenAlex ID: W4415093722