ArticleScience signaling2016
The adaptor protein insulin receptor substrate 2 inhibits alternative macrophage activation and allergic lung inflammation.
Article in Science signaling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
24 citing papers in PubMed, 26 citations in OpenAlex.
- Insulin pathway components and insulin effects on rho kinase in rat colon.Molecular biology reports · 2026Article
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- Epimedin C attenuates airway inflammation and remodeling in Asthma by intervening M2 macrophage polarization via modulating the PI3K/Akt/mTOR signaling pathway.Scientific reports · 2026Article
- Integrated miRNA-mRNA network analysis identifies miR-182-5p as a potential regulator in COPD pathogenesis.Frontiers in medicine · 2026Article
- Maternal Vitamin and Mineral Supplementation Affected Neonatal Gene Expression and Rewired Key Regulatory Genes Underlying Hepatic Metabolism.Animals : an open access journal from MDPI · 2025Article
- Kangayam and Tharparkar cattle exhibit higher duplications in innate immune genes compared to Sahiwal, Gir, Karan Fries, and Holstein Friesian: insights from an array comparative genomic hybridization.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Article
- Adipose tissue macrophages: implications for obesity-associated cancer.Military Medical Research · 2023Review
- The Role of Insulin Receptor Substrate Proteins in Bronchopulmonary Dysplasia and Asthma: New Potential Perspectives.International journal of molecular sciences · 2022Review
- Integrative analysis reveals mouse strain-dependent responses to acute ozone exposure associated with airway macrophage transcriptional activity.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- The inflammatory role of dysregulated IRS2 in pulmonary vascular remodeling under hypoxic conditions.American journal of physiology. Lung cellular and molecular physiology · 2021Article
- Obesity-Associated Myeloid Immunosuppressive Cells, Key Players in Cancer Risk and Response to Immunotherapy.Obesity (Silver Spring, Md.) · 2021Review
- Recent advances in understanding the role of IL-4 signaling.Faculty reviews · 2021Review
- Mechanisms of Dupilumab.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2020Review
- Molecular Response in Intestinal and Immune Tissues toFrontiers in veterinary science · 2020Article
- Deletion of myeloid IRS2 enhances adipose tissue sympathetic nerve function and limits obesity.Molecular metabolism · 2019Article
- Insulin Signaling and Insulin Resistance Facilitate Trained Immunity in Macrophages Through Metabolic and Epigenetic Changes.Frontiers in immunology · 2019Review
- IL-4 and IL-13 Receptor Signaling From 4PS to Insulin Receptor Substrate 2: There and Back Again, a Historical View.Frontiers in immunology · 2018Review
- Coagulation Factor X Regulated by CASC2c Recruited Macrophages and Induced M2 Polarization in Glioblastoma Multiforme.Frontiers in immunology · 2018Article
- Glucocorticoid Receptor ChIP-Seq Identifies PLCD1 as a KLF15 Target that Represses Airway Smooth Muscle Hypertrophy.American journal of respiratory cell and molecular biology · 2017Article
- New perspectives on the regulation of type II inflammation in asthma.F1000Research · 2017Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Insulin receptor substrate 2 (IRS2) is an adaptor protein that becomes tyrosine-phosphorylated in response to the cytokines interleukin-4 (IL-4) and IL-13, which results in activation of the phosphoinositide 3-kinase (PI3K)-Akt pathway. IL-4 and IL-13 contribute to allergic lung inflammation. To examine the role of IRS2 in allergic disease, we evaluated the responses of IRS2-deficient (IRS2(-/-)) mice. Unexpectedly, loss of IRS2 resulted in a substantial increase in the expression of a subset of genes associated with the generation of alternatively activated macrophages (AAMs) in response to IL-4 or IL-13 in vitro. AAMs secrete factors that enhance allergic responses and promote airway remodeling. Moreover, compared to IRS2(+/+) mice, IRS2(+/-) and IRS2(-/-) mice developed enhanced pulmonary inflammation, accumulated eosinophils and AAMs, and exhibited airway and vascular remodeling upon allergen stimulation, responses that partially depended on macrophage-intrinsic IRS2 signaling. Both in unstimulated and IL-4-stimulated macrophages, lack of IRS2 enhanced phosphorylation of Akt and ribosomal S6 protein. Thus, we identified a critical inhibitory loop downstream of IRS2, demonstrating an unanticipated and previously unrecognized role for IRS2 in suppressing allergic lung inflammation and remodeling.
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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.