ArticleProceedings of the National Academy of Sciences of the United States of America2013
Acute inflammation primes myeloid effector cells for anti-inflammatory STAT6 signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- Formyl peptide receptor 1 agonism selectively suppresses mitochondria-driven neutrophil extracellular trap formation while preserving antibacterial immunity.Molecular medicine (Cambridge, Mass.) · 2026Article
- Role of Antibody Glycosylation in Health, Disease, and Therapy.Handbook of experimental pharmacology · 2025Review
- Cytokine polarized, alternatively activated bone marrow neutrophils drive axon regeneration.Nature immunology · 2024Article
- Tim-3Cell death & disease · 2022Article
- Sweet Rules: Linking Glycosylation to Antibody Function.Experientia supplementum (2012) · 2021Review
- IL-4 controls activated neutrophil FcγR2b expression and migration into inflamed joints.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- IL4Rα Signaling Abrogates Hypoxic Neutrophil Survival and Limits Acute Lung Injury ResponsesAmerican journal of respiratory and critical care medicine · 2019Article
- The Regulatory Effects of Interleukin-4 Receptor Signaling on Neutrophils in Type 2 Immune Responses.Frontiers in immunology · 2019Review
- Targeting IgG in Arthritis: Disease Pathways and Therapeutic Avenues.International journal of molecular sciences · 2018Review
- STAT6 and STAT1 Pathway Activation in Circulating Lymphocytes and Monocytes as Predictor of Treatment Response in Rheumatoid Arthritis.PloS one · 2016Article
- Eosinophils and IL-4 Support Nematode Growth Coincident with an Innate Response to Tissue Injury.PLoS pathogens · 2015Article
- IL-37 requires the receptors IL-18Rα and IL-1R8 (SIGIRR) to carry out its multifaceted anti-inflammatory program upon innate signal transduction.Nature immunology · 2015Article
- IFN regulatory factor 8 represses GM-CSF expression in T cells to affect myeloid cell lineage differentiation.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- Signaling by IL-6 promotes alternative activation of macrophages to limit endotoxemia and obesity-associated resistance to insulin.Nature immunology · 2014Article
- IL-4 directly signals tissue-resident macrophages to proliferate beyond homeostatic levels controlled by CSF-1.The Journal of experimental medicine · 2013Article
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
The anti-inflammatory drug high-dose intravenous immunoglobulin, widely used to suppress inflammation, depends on a specific α-2,6-sialylated glycoform of IgG Fc to induce Interleukin 4 (IL-4) and Signal Transducer and Activator of Transcription 6 (STAT6) signaling for its activity. Here we show that anti-inflammatory activities of IL-4 can be attributed to the direct action of this cytokine on myeloid effector cells, depending on their expression of the IL-4 receptor alpha chain (IL-4Rα/CD124). However, in their basal state, these cells express low levels of IL-4Rα and would not be expected to result in significant signaling compared with other cell populations. This apparent paradox can be explained by the observation that during inflammation, triggered by a variety of stimuli (including autoantibodies, adjuvants, and TLR ligands), IL-4Rα is up-regulated specifically on these cells, priming them for STAT6 signaling. The regulation is mediated by a soluble, proteinase K-sensitive factor, released to the circulation by bone marrow-derived, non-B/non-T cells found in several organs, including the lungs, and fat. We propose that this regulation is part of a homeostatic mechanism to limit excessive inflammation and tissue damage. High-dose intravenous immunoglobulin thus exploits an endogenous feedback loop, general to inflammation, that could be further targeted for therapeutic purposes.
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