دورية أكاديمية
Sterile liver injury induces a protective tissue-resident cDC1-ILC1 circuit through cDC1-intrinsic cGAS-STING-dependent IL-12 production.
| العنوان: | Sterile liver injury induces a protective tissue-resident cDC1-ILC1 circuit through cDC1-intrinsic cGAS-STING-dependent IL-12 production. |
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| المؤلفون: | Hildreth AD; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA., Padilla ET; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA., Tafti RY; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA., Legala AR; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA., O'Sullivan TE; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: tosullivan@mednet.ucla.edu. |
| المصدر: | Cell reports [Cell Rep] 2023 Feb 28; Vol. 42 (2), pp. 112141. Date of Electronic Publication: 2023 Feb 18. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 101573691 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2211-1247 (Electronic) NLM ISO Abbreviation: Cell Rep Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Cambridge, MA] : Cell Press, c 2012- |
| مواضيع طبية MeSH: | Immunity, Innate* , Lymphocytes*/metabolism, Humans ; Liver/metabolism ; Inflammation ; Nucleotidyltransferases/metabolism ; Interleukin-12 |
| مستخلص: | Tissue-resident immune cells are critical to the initiation and potentiation of inflammation. However, the tissue-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 connectome 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)-γ 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 production to initiate early protective immune responses. Our study identifies the core communication hubs initiated by tissue-resident innate immune cells during sterile inflammation in vivo and implicates cDC1-derived IL-12 as an important regulator of this process. Competing Interests: Declaration of interests T.E.O is an advisory board member for Modulus Therapeutics and Xyphos, Inc. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.) |
| معلومات مُعتمدة: | F31 DK130585 United States DK NIDDK NIH HHS; R01 AI145997 United States AI NIAID NIH HHS |
| فهرسة مساهمة: | Keywords: CP: Immunology; IL-12; ILC1; cDC1; liver injury; single-cell RNA-seq; sterile inflammation |
| المشرفين على المادة: | EC 2.7.7.- (Nucleotidyltransferases) 187348-17-0 (Interleukin-12) |
| تواريخ الأحداث: | Date Created: 20230222 Date Completed: 20231004 Latest Revision: 20231024 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC10435668 |
| DOI: | 10.1016/j.celrep.2023.112141 |
| PMID: | 36807146 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2211-1247 |
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| DOI: | 10.1016/j.celrep.2023.112141 |