ArticleAllergy2019
IgG4 drives M2a macrophages to a regulatory M2b-like phenotype: potential implication in immune tolerance.
Article in Allergy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- Phenotypic alteration of macrophages during osteoarthritis: a systematic review.Arthritis research & therapy · 2021Pooled it
- Sublingual immunotherapy for 4 years increased the number of Foxp3Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2021Trial
- B cells and humoral immunity in melanoma: regulatory and autoimmune-like features and implications for immunotherapy.Oncoimmunology · 2026Review
- Macrophage programming in systemic sclerosis: Niches, networks, and translational horizons.Seminars in immunopathology · 2026Review
- How to Employ Trained Immunity and Trained Immunity-Based Vaccines to Inhibit Allergic Inflammation.Vaccines · 2026Review
- Immunometabolic programming of macrophages and tumor-associated macrophages: metabolic pathways shaping polarization, immune regulation, and disease outcomes.Frontiers in immunology · 2026Review
- Macrophage plasticity in thyroid eye disease: dual effects of inflammation and fibrosis.Frontiers in immunology · 2026Review
- Influence of extracorporeal shockwaves on macrophage polarization in a 3D collagen matrix.Regenerative therapy · 2025Article
- Fab N-Glycosylation in IgG: Implications in Physiological and Pathological Immune Regulation.Biomolecules · 2025Review
- Dual roles and therapeutic targeting of tumor-associated macrophages in tumor microenvironments.Signal transduction and targeted therapy · 2025Review
- Derlin-3 manipulates the endoplasmic reticulum stress and IgG4 secretion of plasma cells in lung adenocarcinoma.Oncogene · 2025Article
- Unraveling the Roles of Macrophages in Vascularized Composite Allotransplantation.Biomedicines · 2025Review
- Oligonucleotide-Based Modulation of Macrophage Polarization: Emerging Strategies in Immunotherapy.Immunity, inflammation and disease · 2025Review
- Macrophage energy metabolism in cardiometabolic disease.Molecular and cellular biochemistry · 2025Review
- Pharmacological Management of IgG4-Related Disease: From Traditional to Mechanism-Based Targeted Therapies.Drugs & aging · 2025Review
- Tumor-associated macrophages in colon cancer immunotherapy: mechanisms, natural product interventions, and microenvironment remodeling.Frontiers in immunology · 2025Review
- Review
- Fc-Fc interactions and immune inhibitory effects of IgG4: implications for anti-PD-1 immunotherapies.Journal for immunotherapy of cancer · 2024Article
- Research progress on the role of macrophages in acne and regulation by natural plant products.Frontiers in immunology · 2024Review
- The Response of Macrophages in Sepsis-Induced Acute Kidney Injury.Journal of clinical medicine · 2023Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundMacrophages can be converted in vitro into immunoregulatory M2b macrophages in the presence of immune complexes (ICs), but the role of the specific subclasses IgG1 or IgG4 in this phenotypic and functional change is not known.
objectiveWe aimed to refine the original method by applying precisely defined ICs of the subclasses IgG4 or IgG1 constructed by two independent methods.
methodsMonocyte-derived macrophages (MDMs) were treated with M-CSF, followed by IL-4/IL-13 to induce the M2a allergic phenotype. To mimic unspecific or allergen-specific ICs, plates were coated with myeloma IgG1 or IgG4, or with grass pollen allergen Phl p 5 followed by recombinant human Phl p 5-specific IgG1 or IgG4. M2a polarized macrophages were then added, cultured, and examined for cellular markers and cytokines by flow cytometry, ELISA, and rtPCR. Alternatively, immune complexes with IgG1 or IgG4 were formed using protein L.
resultsIgG4 ICs down regulated CD163 and CD206 on M2a cells, and significantly increased IL-10, IL-6, TNFα, and CCL1 secretion, indicating a shift to an M2b-like phenotype. Treatment with IgG4 ICs resulted in expression of FcγRII and down modulation of FcγRII compared with IgG1 treated cells (P = 0.0335) or untreated cells (P < 0.00001).
conclusionImmune complexes with subclasses IgG1 and IgG4 can in vitro be generated by plate absorption, and in fluid form by protein L. Cross-linking of FcγRIIb by the IgG4 subclass redirects pro-allergic M2a macrophages to an M2b-like immunosuppressive phenotype. This suggests an interplay of macrophages with IgG4 in immune tolerance, likely relevant in allergen immunotherapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.