ArticleThe Journal of clinical investigation2006
The IL-21 receptor augments Th2 effector function and alternative macrophage activation.
Article in The Journal of clinical investigation, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 168 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
168 citing papers in PubMed, 1 synthesis or guideline pooled it, 340 citations in OpenAlex.
- Crosstalk between fibroblasts and immunocytes in fibrosis: From molecular mechanisms to clinical trials.Clinical and translational medicine · 2024Pooled it
- HIF-2α induction in de novo lipogenesis in metabolic dysfunction-associated steatohepatitis is dependent on IL-21 signaling.The Journal of biological chemistry · 2026Article
- Airway Goblet Metaplasia Resulting from YAP/TAZ Deletion Drives Pulmonary Inflammatory Responses.American journal of respiratory cell and molecular biology · 2026Article
- Review
- Design of a potent interleukin-21 mimic for cancer immunotherapy.Science immunology · 2025Article
- IL-4 and TGF-β regulate inflammatory cytokines and cellular infiltration in the lung and systemic IL-6 in mouse-adapted SARS-CoV-2 infection.ImmunoHorizons · 2025Article
- Identification of M1 macrophage infiltration-related genes for immunotherapy in Her2-positive breast cancer based on bioinformatics analysis and machine learning.Scientific reports · 2025Article
- Advanced Immunomodulatory Biomaterials for Therapeutic Applications.Advanced healthcare materials · 2025Review
- Macrophages as Multifaceted Orchestrators of Tissue Repair: Bridging Inflammation, Regeneration, and Therapeutic Innovation.Journal of inflammation research · 2025Review
- IL-2 family cytokines IL-9 and IL-21 differentially regulate innate and adaptive type 2 immunity in asthma.The Journal of allergy and clinical immunology · 2024Article
- Monocyte-macrophages modulate intestinal homeostasis in inflammatory bowel disease.Biomarker research · 2024Review
- An IL-17A-centric response to Epstein-Barr virus DNA mediated by dendritic Cell-T cell interactions.Frontiers in molecular biosciences · 2024Article
- Immune and non-immune mediators in the fibrosis pathogenesis of salivary gland in Sjögren's syndrome.Frontiers in immunology · 2024Review
- Lipid metabolic reprogramming of hepatic CD4Microbiology spectrum · 2023Article
- T Follicular Helper Cells in Tertiary Lymphoid Structure Contribute to Renal Fibrosis by IL-21.International journal of molecular sciences · 2023Article
- Cellular mechanotransduction in health and diseases: from molecular mechanism to therapeutic targets.Signal transduction and targeted therapy · 2023Review
- Role of tumor-associated macrophages in common digestive system malignant tumors.World journal of gastrointestinal oncology · 2023Review
- Transcriptomic signatures reveal a shift towards an anti-inflammatory gene expression profile but also the induction of type I and type II interferon signaling networks through aryl hydrocarbon receptor activation in murine macrophages.Frontiers in immunology · 2023Article
- Immune modulation of Th1/Th2/Treg/Th17/Th9/Th21 cells in rabbits infected withFrontiers in cellular and infection microbiology · 2023Article
- Engineered exosomes for studies in tumor immunology.Immunological reviews · 2022Review
108 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
The IL-21 receptor (IL-21R) shows significant homology with the IL-4R, and CD4+ Th2 cells are an important source of IL-21. Here we examined whether the IL-21R regulates the development of Th2 responses in vivo. To do this, we infected IL-21R-/- mice with the Th2-inducing pathogens Schistosoma mansoni and Nippostrongylus brasiliensis and examined the influence of IL-21R deficiency on the development of Th2-dependent pathology. We showed that granulomatous inflammation and liver fibrosis were significantly reduced in S. mansoni-infected IL-21R-/- mice and in IL-21R+/+ mice treated with soluble IL-21R-Fc (sIL-21R-Fc). The impaired granulomatous response was also associated with a marked reduction in Th2 cytokine expression and function, as evidenced by the attenuated IL-4, IL-13, AMCase, Ym1, and FIZZ1 (also referred to as RELMalpha) responses in the tissues. A similarly impaired Th2 response was observed following N. brasiliensis infection. In vitro, IL-21 significantly augmented IL-4Ralpha and IL-13Ralpha1 expression in macrophages, resulting in increased FIZZ1 mRNA and arginase-1 activity following stimulation with IL-4 and IL-13. As such, these data identify the IL-21R as an important amplifier of alternative macrophage activation. Collectively, these results illustrate an essential function for the IL-21R in the development of pathogen-induced Th2 responses, which may have relevance in therapies for both inflammatory and chronic fibrotic diseases.
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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.