Journal
CELL REPORTS
Volume 42, Issue 2, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2023.112141
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Using single-cell transcriptomic analysis, the study reveals the liver-resident cell connectome and signalome during acute liver injury. The results identify Il12b as a central regulator of liver injury-associated changes in gene expression. It is found that Interleukin (IL)-12 produced by conventional type 1 dendritic cells (cDC1s) is required for protection during acute injury through activation of interferon (IFN)-g production by liver-resident type 1 innate lymphoid cells (ILC1s). The study also uncovers the role of cDC1-intrinsic cGAS-STING signaling in initiating early protective immune responses via IL-12 production.
Tissue-resident immune cells are critical to the initiation and potentiation of inflammation. However, the tis-sue-protective cellular communication networks initiated by resident immunity during sterile inflammation are not well understood. Using single-cell transcriptomic analysis, we show the liver-resident cell connec-tome and signalome during acute liver injury. These analyses identify Il12b as a central regulator of liver injury-associated changes in gene expression. Interleukin (IL)-12 produced by conventional type 1 dendritic cells (cDC1s) is required for protection during acute injury through activation of interferon (IFN)-g production by liver-resident type 1 innate lymphoid cells (ILC1s). Using a targeted in vivo CRISPR-Cas9 screen of innate immune sensing pathways, we find that cDC1-intrinsic cGAS-STING signaling acts upstream of IL-12 pro-duction to initiate early protective immune responses. Our study identifies the core communication hubs initi-ated by tissue-resident innate immune cells during sterile inflammation in vivo and implicates cDC1-derived IL-12 as an important regulator of this process.
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