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Updated: Sep 16, 2026

Long Term Intravital Multiphoton Microscopy Imaging of Immune Cells in Healthy and Diseased Liver Using CXCR6.Gfp Reporter Mice
Published on: March 24, 2015
Interferon-λ Receptor Positive Monocytes/Macrophages Orchestrate a Pro-fibrotic Immune Environment in Hepatitis B
Abstract:
Interferon-λ receptor (IFNLR), a heterodimer composed of IFNLR1 and IL‑10Rβ, mediates IFN‑λ‑driven fibrotic effects. This study investigated the involvement of IFNLR1+ monocytes/macrophages in orchestrating pro-fibrotic immune microenvironment. Flow cytometric analysis of peripheral blood showed that IFNLR1⁺ monocytes were elevated in patients with chronic hepatitis B virus (HBV) infection (CHI) and patients with HBV‑related liver cirrhosis (LC), compared with healthy control (HC). These cells also displayed a CCR2ʰⁱCCR5ʰⁱCX3CR1ʰⁱCD86ʰⁱHLA-DRʰⁱCD163ʰⁱMERTKʰⁱ phenotype with an IL‑10ʰⁱTNF‑αʰⁱ cytokine profile. Hepatic fibrosis was induced in wild‑type and Ifnlr1‑knockout (Ifnlr1-/-) mice using carbon tetrachloride and recombinant adeno‑associated virus 8‑1.3HBV. Ifnlr1 deficiency downregulated CCR2 and CCR5 expression on monocytes/macrophages, attenuated collagen deposition, but enhanced HBV-DNA replication. In vitro, bone marrow derived macrophages (BMDMs) were co-cultured with hepatic stellate cells (HSCs) or naive CD4+ T cells to assess the functional impact of IFNLR1+ macrophages. Concurrently, the involvement of lipid metabolism in IFN‑λ/IFNLR1‑mediated macrophage regulation was examined using liver X receptor (LXR) agonists/antagonists. Ifnlr1-/- BMDMs exhibited a diminished capacity to activate HSCs and drive regulatory T cells differentiation. Mechanistically, IFN-λ-IFNLR1 signaling suppressed LXR-dependent lipid metabolism, thereby promoting tumor necrosis factor (TNF)-α and IL-1β production, and LXR pathway inhibition favored M1-macrophage polarization. Collectively, IFNLR1 identifies a pro-fibrotic and immunoregulatory monocyte/macrophage subset. Targeting IFNLR1-LXR axis may represent promising anti-fibrotic strategies for HBV-related liver fibrosis.
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