Type I interferon signaling facilitates resolution of acute liver injury by priming macrophage polarization.
Cell Mol Immunol, 2023/02;20(2):143-157.
Song Q[1], Datta S[2], Liang X[3], Xu X[1], Pavicic P[2], Zhang X[4], Zhao Y[5], Liu S[4], Zhao J[4], Xu Y[4], Xu J[4], Wu L[4], Wu Z[4], Zhang M[4], Zhao Z[1], Lin C[6], Wang Y[7], Han P[3], Jiang P[5], Qin Y[3], Li W[5], Zhang Y[3], Luo Y[3], Sen G[2], Stark GR[7], Zhao C[8, 9], Hamilton T[10], Yang J[11, 12]
Affiliations
PMID: 36596875DOI: 10.1038/s41423-022-00966-y
Impact factor: 22.096
Abstract
Due to their broad functional plasticity, myeloid cells contribute to both liver injury and recovery during acetaminophen overdose-induced acute liver injury (APAP-ALI). A comprehensive understanding of cellular diversity and intercellular crosstalk is essential to elucidate the mechanisms and to develop therapeutic strategies for APAP-ALI treatment. Here, we identified the function of IFN-I in the myeloid compartment during APAP-ALI. Utilizing single-cell RNA sequencing, we characterized the cellular atlas and dynamic progression of liver CD11b+ cells post APAP-ALI in WT and STAT2 T403A mice, which was further validated by immunofluorescence staining, bulk RNA-seq, and functional experiments in vitro and in vivo. We identified IFN-I-dependent transcriptional programs in a three-way communication pathway that involved IFN-I synthesis in intermediate restorative macrophages, leading to CSF-1 production in aging neutrophils that ultimately enabled Trem2+ restorative macrophage maturation, contributing to efficient liver repair. Overall, we uncovered the heterogeneity of hepatic myeloid cells in APAP-ALI at single-cell resolution and the therapeutic potential of IFN-I in the treatment of APAP-ALI.
Keywords: APAP-ALI; CSF1+ neutrophil; IFN-I; Macrophage polarization; STAT2 T403 phosphorylation; scRNA-seq
MeSH terms
Animals; Mice; Acetaminophen; Chemical and Drug Induced Liver Injury; Liver; Neutrophils; Macrophages; Mice, Inbred C57BL; Membrane Glycoproteins; Receptors, Immunologic
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