ArticleeLife2021
Integration of IL-2 and IL-4 signals coordinates divergent regulatory T cell responses and drives therapeutic efficacy.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
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
28 citing papers in PubMed, 47 citations in OpenAlex.
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- Roles of interleukins in spasmolytic polypeptide‑expressing metaplasia (Review).International journal of oncology · 2026Review
- Optoregulated mRNA Delivery Controls Pleiotropic Immune Signaling for Tumor-Targeted Therapy.Angewandte Chemie (International ed. in English) · 2025Article
- T Regulatory Mechanisms in Airway and Interstitial Lung Disease.Seminars in respiratory and critical care medicine · 2025Review
- The role of mesenchymal stem cell‑derived exosomes in asthma (Review).Molecular medicine reports · 2025Review
- RGS2 is an innate immune checkpoint for suppressing Gαq-mediated IFNγ generation and lung injury.iScience · 2025Article
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- Oral administration of glycyrrhizic acid with intramuscular injection of foot-and-mouth disease vaccine enhances the adaptive immune system.Frontiers in microbiology · 2025Article
- Impact of immunosuppressants on tumor pulmonary metastasis: new insight into transplantation for hepatocellular carcinoma.Cancer biology & medicine · 2024Review
- Age-dependent Powassan virus lethality is linked to glial cell activation and divergent neuroinflammatory cytokine responses in a murine model.Journal of virology · 2024Article
- Lymphotoxin limits Foxp3Nature communications · 2024Article
- Next-generation probiotic candidates targeting intestinal health in weaned piglets: Both live and heat-killedAnimal nutrition (Zhongguo xu mu shou yi xue hui) · 2024Article
- Coinhibitory Molecule VISTA Play an Important Negative Regulatory Role in the Immunopathology of Bronchial Asthma.Journal of asthma and allergy · 2024Article
- Deciphering the developmental trajectory of tissue-resident Foxp3Frontiers in immunology · 2024Review
- The Cytokine Profile in Different Stages of Schistosomiasis Japonica.Pathogens (Basel, Switzerland) · 2023Article
- Intestinal Tr1 Cells Confer Protection against Colitis in the Absence of Foxp3+ Regulatory T Cell-Derived IL-10.ImmunoHorizons · 2023Article
- Targeted Lipidomics and Inflammation Response to Six Weeks of Sprint Interval Training in Male Adolescents.International journal of environmental research and public health · 2023Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Cells exist within complex milieus of communicating factors, such as cytokines, that combine to generate context-specific responses, yet nearly all knowledge about the function of each cytokine and the signaling propagated downstream of their recognition is based on the response to individual cytokines. Here, we found that regulatory T cells (Tregs) integrate concurrent signaling initiated by IL-2 and IL-4 to generate a response divergent from the sum of the two pathways in isolation. IL-4 stimulation of STAT6 phosphorylation was blocked by IL-2, while IL-2 and IL-4 synergized to enhance STAT5 phosphorylation, IL-10 production, and the selective proliferation of IL-10-producing Tregs, leading to increased inhibition of conventional T cell activation and the reversal of asthma and multiple sclerosis in mice. These data define a mechanism of combinatorial cytokine signaling and lay the foundation upon which to better understand the origins of cytokine pleiotropy while informing improved the clinical use of cytokines.
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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.