ArticleArthritis research & therapy2021
Pathogenic roles and therapeutic potential of the CCL8-CCR8 axis in a murine model of IgG4-related sialadenitis.
Article in Arthritis research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 23 citations in OpenAlex.
- Pathogenesis exploration of lgG4-related disease: From the traditional central dogma and its remodeling perspective.Chinese medical journal · 2026Review
- From inflammatory initiation to fibrotic remodeling: mechanisms and precision therapeutic strategies in otorhinolaryngologic involvement of IgG4-related disease.Frontiers in medicine · 2026Review
- Beyond the Th2 paradigm: CD4+ cytotoxic T lymphocytes as key drivers of tissue damage and fibrosis in IgG4-related disease.Frontiers in immunology · 2026Review
- Reference-guided computational framework identifies microenvironment metabolic subtypes and targets using pan-cancer single-cell datasets.Genome medicine · 2025Article
- T follicular helper 1 cells in blood potentially mirror salivary gland-infiltrating T cells in Sjögren's disease.Scientific reports · 2025Article
- IgG4-related Disease: Recent Topics on Immunological Aspects of This Disorder and Their Application in New Treatment Strategies.Internal medicine (Tokyo, Japan) · 2025Review
- Defective LAT signalosome pathology in mice mimics human IgG4-related disease at single-cell level.The Journal of experimental medicine · 2023Article
- Oxamate enhances the efficacy of CAR-T therapy against glioblastoma via suppressing ectonucleotidases and CCR8 lactylation.Journal of experimental & clinical cancer research : CR · 2023Article
- Hypoxic niches attract and sequester tumor-associated macrophages and cytotoxic T cells and reprogram them for immunosuppression.Immunity · 2023Article
- TSLP promoting B cell proliferation and polarizing follicular helper T cell as a therapeutic target in IgG4-related disease.Journal of translational medicine · 2022Article
- Potential roles of non-lymphocytic cells in the pathogenesis of IgG4-related disease.Frontiers in immunology · 2022Review
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOur previous studies reveal that CCL18-CCR8 chemokine axis is upregulated in patients of immunoglobulin G4-related disease (IgG4-RD), suggesting that the CCL18-CCR8 axis is implicated in the etiology of IgG4-RD, although whether this axis has a potential as a therapeutic target remains unclear. Our purpose was to clarify the pathogenic roles and therapeutic potential of the murine CCL8 (analog of human CCL18)-CCR8 axis by using an animal model of IgG4-RD (LAT Y136F knockin mice; LAT mice).
methodsWe compared the infiltration of inflammatory cells and the fibrosis of the salivary glands of 6-week-old LAT mice and littermate mice. The expressions of Ccl8 and Ccr8 were also compared. Next, we investigated the therapeutic effects of intravenous administration of anti-CCL8 neutralizing antibody in LAT mice against inflammation and fibrosis of the salivary glands. We also investigated the effects of stimulation with recombinant mouse CCL8 on the collagen production in a mouse fibroblast cell line (NIH/3 T3) in vitro.
resultsWhen compared with the littermates, the LAT mice showed apparent infiltration of inflammatory cells and fibrosis in the salivary glands. The focus and fibrosis score in the salivary glands were significantly higher in the LAT mice than in the littermates. The expression levels of Ccl8 in the spleen and of Ccr8 in the salivary glands were significantly higher in the LAT mice than in the littermates. Anti-CCL8 antibody significantly improved the focus and fibrosis score in the salivary glands of the LAT mice. In vitro, stimulation with recombinant mouse CCL8 significantly increased the expression of collagen and ERK1/2 phosphorylation in NIH/3 T3.
conclusionWe clarified the overexpression and therapeutic potential of the mouse CCL8-CCR8 axis in LAT mice, which could play a crucial role in fibrosis via ERK1/2 phosphorylation, as well as the chemotaxis of inflammatory cells. The human CCL18-CCR8 axis might be a novel therapeutic target for IgG4-RD.
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