You are currently viewing the abstract.
View Full TextLog in to view the full text
AAAS login provides access to Science for AAAS members, and access to other journals in the Science family to users who have purchased individual subscriptions.
More options
Download and print this article for your personal scholarly, research, and educational use.
Buy a single issue of Science for just $15 USD.
Cardioprotective myeloid cells
Acute ischemic injury to the heart precipitates a strong inflammatory response including influx of myeloid cells expressing type I interferon–stimulated genes (ISGs). Calcagno et al. used single-cell RNA sequencing to probe the origin, evolution, and heterogeneity of this response in the first 4 days after myocardial infarction using human and mouse myeloid cells. Induction of ISG in myeloid cells was initially observed in bone marrow and blood. Post-infarct cardiac tissue in mice contained myeloid subsets with and without ISG expression and a steady-state macrophage population with Nrf2-dependent anti-inflammatory activity. On the basis of their findings, the authors developed an ISG score as a potential biomarker to assess how the vigor of type I interferon signaling influences clinical outcomes after a heart attack.
Abstract
Sterile tissue injury is thought to locally activate innate immune responses via damage-associated molecular patterns (DAMPs). Whether innate immune pathways are remotely activated remains relatively unexplored. Here, by analyzing ~145,000 single-cell transcriptomes at steady state and after myocardial infarction (MI) in mice and humans, we show that the type I interferon (IFN) response, characterized by expression of IFN-stimulated genes (ISGs), begins far from the site of injury, in neutrophil and monocyte progenitors within the bone marrow. In the peripheral blood of patients, we observed defined subsets of ISG-expressing neutrophils and monocytes. In the bone marrow and blood of mice, ISG expression was detected in neutrophils and monocytes and their progenitors, intensified with maturation at steady-state and after MI, and was controlled by Tet2 and Irf3 transcriptional regulators. Within the infarcted heart, ISG-expressing cells were negatively regulated by Nrf2 activation in Ccr2− steady-state cardiac macrophages. Our results show that IFN signaling begins in the bone marrow, implicate multiple transcriptional regulators (Tet2, Irf3, and Nrf2) in governing ISG expression, and provide a clinical biomarker (ISG score) for studying IFN signaling in patients.
- Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works
This is an article distributed under the terms of the Science Journals Default License.
