ArticleArthritis & rheumatology (Hoboken, N.J.)2020
Activated M2 Macrophages Contribute to the Pathogenesis of IgG4-Related Disease via Toll-like Receptor 7/Interleukin-33 Signaling.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 79 citations in OpenAlex.
- Anti-human TLR7 antibody for therapeutic intervention in systemic lupus erythematosus.International immunology · 2026Article
- From inflammatory initiation to fibrotic remodeling: mechanisms and precision therapeutic strategies in otorhinolaryngologic involvement of IgG4-related disease.Frontiers in medicine · 2026Review
- IgG4-Related Disease: Emerging Roles of Novel Genetic Variants, Immune Cell Subsets and Therapeutic Targets.Allergy · 2025Review
- Whole tissue spatial cellular analysis reveals increased macrophage infiltration in pancreata of autoantibody positive donors and patients with type 1 diabetes.bioRxiv : the preprint server for biology · 2025Article
- IgG4-Related Cholangitis.Seminars in liver disease · 2025Review
- Unraveling the Microenvironment and the Pathogenic Axis of HIF-1α-Visfatin-Fibrosis in Autoimmune Pancreatitis Using a Single-Cell Atlas.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Treatment Strategies for Chronic Pancreatitis (CP).Pharmaceuticals (Basel, Switzerland) · 2025Review
- IgG4-related disease presenting with hypercalcemia: case report and mechanistic insights.Frontiers in immunology · 2025Article
- Integrated analysis of M2 macrophage-related gene prognostic model and single-cell sequence to predict immunotherapy response in lung adenocarcinoma.Frontiers in genetics · 2025Article
- Immune cell crosstalk between ANCA-associated vasculitis and IgG4-related disease: an unresolved pathogenic link.Frontiers in immunology · 2025Review
- IgG4-related Disease: Recent Topics on Immunological Aspects of This Disorder and Their Application in New Treatment Strategies.Internal medicine (Tokyo, Japan) · 2025Review
- Interleukin-33 and Obesity-Related Inflammation and Cancer.Encyclopedia · 2024Article
- Myofibroblast and pro-fibrotic cytokines in fibrosis of IgG4-related disease (IgG4-RD) patients from South Asia: preliminary data.Clinical rheumatology · 2024Article
- Immune and non-immune mediators in the fibrosis pathogenesis of salivary gland in Sjögren's syndrome.Frontiers in immunology · 2024Review
- Toll-like receptors 2 and 4, and bacterial proteins in IgG4-related sialadenitis, other types of chronic sialadenitis and sialolithiasis.Journal of oral microbiology · 2024Article
- Toll-like receptor 9-positive plasmacytoid dendritic cells promote Th17 immune responses in oral lichen planus stimulated by epithelium-derived cathepsin K.Scientific reports · 2023Article
- Single-cell transcriptome analysis and protein profiling reveal broad immune system activation in IgG4-related disease.JCI insight · 2023Article
- Single-Cell RNA-Sequencing Reveals Peripheral T Helper Cells Promoting the Development of IgG4-Related Disease by Enhancing B Cell Activation and Differentiation.International journal of molecular sciences · 2023Article
- Implication of allergy and atopy in IgG4-related disease.The World Allergy Organization journal · 2023Review
- Uncovering the Spectrum of Hemophagocytic Lymphohistiocytosis: A Nephrology Department's Analysis of 14 Cases.Clinical medicine insights. Case reports · 2023Review
Corrections and comments
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Authors and funding
22 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveIgG4-related disease (IgG4-RD) is a unique inflammatory disorder in which Th2 cytokines promote IgG4 production. In addition, recent studies have implicated the Toll-like receptor (TLR) pathway. This study was undertaken to examine the expression of TLRs in salivary glands (SGs) from patients with IgG4-RD.
methodsSGs from 15 patients with IgG4-RD, 15 patients with Sjögren's syndrome (SS), 10 patients with chronic sialadenitis, and 10 healthy controls were examined histologically. TLR family gene expression (TLR-1 through TLR-10) was analyzed by DNA microarray in the submandibular glands (SMGs). Up-regulation of TLRs was confirmed in SGs from patients with IgG4-RD. Finally, the phenotype of human TLR-7 (huTLR-7)-transgenic C57BL/6 mice was assessed before and after stimulation with TLR agonist.
resultsIn patients with IgG4-RD, TLR-4, TLR-7, TLR-8, and TLR-9 were overexpressed. Polymerase chain reaction validated the up-regulation of TLR-7 in IgG4-RD compared with the other groups. Immunohistochemical analysis confirmed strong infiltration of TLR-7-positive cells in the SGs of patients with IgG4-RD. Double immunohistochemical staining showed that TLR-7 expression colocalized with CD163+ M2 macrophages. After in vitro stimulation with a TLR-7 agonist, CD163+ M2 macrophages produced higher levels of interleukin-33 (IL-33), which is a Th2-activating cytokine. In huTLR-7-transgenic mice, the focus and fibrosis scores in SMGs, pancreas, and lungs were significantly higher than those in wild-type mice (P < 0.05). Moreover, the concentration of serum IgG, IgG1, and IL-33 in huTLR-7-transgenic mice was distinctly increased upon stimulation with a TLR-7 agonist (P < 0.05).
conclusionTLR-7-expressing M2 macrophages may promote the activation of Th2 immune responses via IL-33 secretion in IgG4-RD.
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