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Virus-associated inflammation imprints an inflammatory profile on monocyte-derived macrophages in the human liver

Chronic liver injury triggers the activation and recruitment of immune cells, causing antigen-independent tissue damage and liver disease progression. Tissue inflammation can reshape macrophage composition through monocyte replacement. Replacement of tissue macrophages with monocytes differentiating...

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Hauptverfasser: Sanchez Vasquez, Juan Diego (VerfasserIn) , Nkongolo, Shirin (VerfasserIn) , Traum, Daniel (VerfasserIn) , Sotov, Valentin (VerfasserIn) , Kim, Samuel C. (VerfasserIn) , Mahamed, Deeqa (VerfasserIn) , Mehrotra, Aman (VerfasserIn) , Patel, Anjali (VerfasserIn) , Chen, Diana Y. (VerfasserIn) , Fung, Scott (VerfasserIn) , Gaggar, Anuj (VerfasserIn) , Feld, Jordan J. (VerfasserIn) , Chang, Kyong-Mi (VerfasserIn) , Wallin, Jeffrey J. (VerfasserIn) , Wang, Ben X. (VerfasserIn) , Janssen, Harry L. A. (VerfasserIn) , Gehring, Adam J. (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: April 15, 2025
In: The journal of clinical investigation
Year: 2025, Jahrgang: 135, Heft: 8, Pages: 1-14
ISSN:1558-8238
DOI:10.1172/JCI175241
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.1172/JCI175241
Verlag, kostenfrei, Volltext: https://www.jci.org/articles/view/175241#SEC5
Volltext
Verfasserangaben:Juan Diego Sanchez Vasquez, Shirin Nkongolo, Daniel Traum, Valentin Sotov, Samuel C. Kim, Deeqa Mahamed, Aman Mehrotra, Anjali Patel, Diana Y. Chen, Scott Fung, Anuj Gaggar, Jordan J. Feld, Kyong-Mi Chang, Jeffrey J. Wallin, Ben X. Wang, Harry L.A. Janssen, and Adam J. Gehring
Beschreibung
Zusammenfassung:Chronic liver injury triggers the activation and recruitment of immune cells, causing antigen-independent tissue damage and liver disease progression. Tissue inflammation can reshape macrophage composition through monocyte replacement. Replacement of tissue macrophages with monocytes differentiating in an inflammatory environment can potentially imprint a phenotype that switches the liver from an immune-tolerant organ to one predisposed to tissue damage. We longitudinally sampled the liver of patients with chronic hepatitis B who had active liver inflammation and were starting antiviral therapy. Antiviral therapy suppressed viral replication and liver inflammation, which coincided with decreased myeloid activation markers. Single-cell RNA-Seq mapped peripheral inflammatory markers to a monocyte-derived macrophage population, distinct from Kupffer cells, with an inflammatory transcriptional profile. The inflammatory macrophages (iMacs) differentiated from blood monocytes and were unique from macrophage found in healthy or cirrhotic liver. iMacs retained their core transcriptional signature after inflammation resolved, indicating inflammation-mediated remodeling of the macrophage population in the human liver that may affect progressive liver disease and immunotherapy.
Beschreibung:Gesehen am 12.01.2026
Beschreibung:Online Resource
ISSN:1558-8238
DOI:10.1172/JCI175241

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