ArticleJCI insight2019
PP2A enables IL-2 signaling by preserving IL-2Rβ chain expression during Treg development.
Article in JCI insight, 2019. 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, 23 citations in OpenAlex.
- AT2R activation reduces M1-type macrophages and promotes tregs accumulation in ischemia-reperfusion-induced acute kidney injury.Frontiers in pharmacology · 2026Article
- IFI27-mediated regulation of regulatory T cells aggravates lung injury in sepsis via IL-10/STAT3 signaling.Frontiers in immunology · 2026Article
- Protein phosphatases in systemic autoimmunity.Immunometabolism (Cobham, Surrey) · 2025Review
- Targeting a disintegrin and metalloprotease (ADAM) 17-CD122 axis enhances CD8Signal transduction and targeted therapy · 2024Article
- A Disintegrin and metalloproteinase carves T cell abnormalities and pathogenesis in systemic lupus erythematosus.Clinical immunology (Orlando, Fla.) · 2024Review
- Interleukin-2 signaling in the regulation of T cell biology in autoimmunity and cancer.Immunity · 2024Review
- Role of Treg cell subsets in cardiovascular disease pathogenesis and potential therapeutic targets.Frontiers in immunology · 2024Review
- "IL-2 immunotherapy for targeting regulatory T cells in autoimmunity".Genes and immunity · 2023Review
- Comparative Evaluation of Synthetic Cytokines for Enhancing Production and Performance of NK92 Cell-Based Therapies.GEN biotechnology · 2023Article
- Functional roles of sphingolipids in immunity and their implication in disease.Experimental & molecular medicine · 2023Review
- Targeting protein phosphatases in cancer immunotherapy and autoimmune disorders.Nature reviews. Drug discovery · 2023Review
- Protein Phosphatase 2A: Role in T Cells and Diseases.Journal of immunology research · 2023Review
- Low-Dose IL-2 Attenuated Depression-like Behaviors and Pathological Changes through Restoring the Balances between IL-6 and TGF-β and between Th17 and Treg in a Chronic Stress-Induced Mouse Model of Depression.International journal of molecular sciences · 2022Article
- Genetic Variations Controlling Regulatory T Cell Development and Activity in Mouse Models of Lupus-Like Autoimmunity.Frontiers in immunology · 2022Review
- ADAM9 enhances Th17 cell differentiation and autoimmunity by activating TGF-β1.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- PPP2R2D suppresses IL-2 production and Treg function.JCI insight · 2020Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 2 countries.
Funding
Abstract
Tregs require IL-2 signaling for signal transducer and activator of transcription 5 (STAT5)-mediated induction of Foxp3. While phosphatase 2A (PP2A) is a negative regulator of IL-2 production in effector T cells and Tregs do not produce IL-2, it is not known whether PP2A controls IL-2 signaling in Tregs. To address the role of PP2A in IL-2 signaling in Tregs we studied mice engineered to lack PP2A in all Foxp3-expressing cells. We report that PP2A is required to enable Foxp3 expression and to maintain sufficient numbers of Tregs in the thymus. We show for the first time that PP2A prevents the selective loss of surface IL-2Rβ and preserves IL-2R signaling potency in Tregs. The loss of IL-2Rβ in thymus- and spleen-derived Tregs that lack PP2A is due to increased sheddase activity. Pan-sheddase or selective A disintegrin and metalloproteinase 10 (ADAM10) inhibition, like forced expression of IL-2Rβ in PP2A-deficient Tregs restored IL-2Rβ expression and signaling. Thus, PP2A restrains the sheddase activity of ADAM10 in Treg cells to prevent the cleavage of IL-2Rβ from the cell surface to enable competent IL-2R signaling which is essential for Tregs development and homeostasis.
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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.