ArticleThe Journal of biological chemistry2022
The metalloprotease ADAM10 generates soluble interleukin-2 receptor alpha (sCD25) in vivo.
Article in The Journal of biological chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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13 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Soluble PD-L1 changes in advanced non-small cell lung cancer patients treated with PD-1 inhibitors: an individual patient data meta-analysis.Frontiers in immunology · 2023Pooled it
- Peripheral blood IFN-γ-producing T-cell subsets and soluble IL-2 receptor as independent prognostic biomarkers in NSCLC treated with immune checkpoint inhibitor-based therapy.Discover oncology · 2026Article
- Scube2 primes Dispatched and ADAM10-mediated Shh release by recruiting HDL acceptors to the plasma membrane.Communications biology · 2026Article
- Adherent Natural Killer Cells De Novo Express IL-2Rα and Sustain Long-Lasting, Potent Anti-Tumor Activity in Picomolar Concentrations of IL-2.Journal of cancer immunology · 2025Article
- The aging heart: exploring the role of Klotho in cardiac health/function.The journal of cardiovascular aging · 2024Article
- A Disintegrin and metalloproteinase carves T cell abnormalities and pathogenesis in systemic lupus erythematosus.Clinical immunology (Orlando, Fla.) · 2024Review
- The role of NF-κB in carcinogenesis of cervical cancer: opportunities and challenges.Molecular biology reports · 2024Review
- A type I interferon regulatory network for human plasmacytoid dendritic cells based on heparin, membrane-bound and soluble BDCA-2.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Diagnostic value of soluble Interleukin-2 receptor in patients suffering neurosarcoidosis: A systematic review.Journal of central nervous system disease · 2024Review
- IL-2 based cancer immunotherapies: an evolving paradigm.Frontiers in immunology · 2024Review
- Long-term increase in soluble interleukin-6 receptor levels in convalescents after mild COVID-19 infection.Frontiers in immunology · 2024Article
- Clinical roles of soluble PD-1 and PD-L1 in plasma of NSCLC patients treated with immune checkpoint inhibitors.Cancer immunology, immunotherapy : CII · 2023Article
- Reigniting hope in cancer treatment: the promise and pitfalls of IL-2 and IL-2R targeting strategies.Molecular cancer · 2023Review
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cytokine interleukin-2 (IL-2) plays a critical role in controlling the immune homeostasis by regulating the proliferation and differentiation of immune cells, especially T cells. IL-2 signaling is mediated via the IL-2 receptor (IL-2R) complex, which consists of the IL-2Rα (CD25), the IL-2Rβ, and the IL-2Rγ. While the latter are required for signal transduction, IL-2Rα controls the ligand-binding affinity of the receptor complex. A soluble form of the IL-2Rα (sIL-2Rα) is found constitutively in human serum, though its levels are increased under various pathophysiological conditions. The sIL-2Rα originates partly from activated T cells through proteolytic cleavage, but neither the responsible proteases nor stimuli that lead to IL-2Rα cleavage are known. Here, we show that the metalloproteases ADAM10 and ADAM17 can cleave the IL-2Rα and generate a soluble ectodomain, which functions as a decoy receptor that inhibits IL-2 signaling in T cells. We demonstrate that ADAM10 is mainly responsible for constitutive shedding of the IL-2Rα, while ADAM17 is involved in IL-2Rα cleavage upon T cell activation. In vivo, we found that mice with a CD4-specific deletion of ADAM10, but not ADAM17, show reduced steady-state sIL-2Rα serum levels. We propose that the identification of proteases involved in sIL-2Rα generation will allow for manipulation of IL-2Rα cleavage, especially as constitutive and induced cleavage of IL-2Rα are executed by different proteases, and thus offer a novel opportunity to alter IL-2 function.
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