ArticleThe Journal of experimental medicine2013
Epidermal IL-15Rα acts as an endogenous antagonist of psoriasiform inflammation in mouse and man.
Article in The Journal of experimental medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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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
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
32 citing papers in PubMed, 67 citations in OpenAlex.
- Phase 2 trial (NCI-COTC030) of adjuvant inhaled recombinant human IL-15 combined with amputation and adjuvant chemotherapy in dogs with appendicular osteosarcoma.Frontiers in immunology · 2025Trial
- Article
- High Humidity Exacerbates Psoriasiform Skin Disease Relapse by Increasing Tissue-Resident Memory T Cells via Altering Skin Microbiota.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Interleukin 15 and autoimmune disorders: pathophysiology, therapeutic potential, and clinical implications.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- IL-15 Promotes the Survival of Anti-Inflammatory (M2), Immunoinhibitory (IL-10+) Dermal Macrophages in Human Eyelid Skin Under IFNγ-Dominated Inflammatory Conditions.International journal of molecular sciences · 2025Article
- Immunometabolic Approaches Mitigating Foreign Body Response and Transcriptome Characterization of the Foreign Body Capsule.Advanced healthcare materials · 2025Article
- Transpresentation of interleukin 15 by stromal cell subsets regulates immune cell homeostasis.Frontiers in immunology · 2025Article
- Multi-System-Level Analysis Reveals Differential Expression of Stress Response-Associated Genes in Inflammatory Solar Lentigo.International journal of molecular sciences · 2024Article
- Biased IL-2 signals induce Foxp3-rich pulmonary lymphoid structures and facilitate long-term lung allograft acceptance in mice.Nature communications · 2023Article
- The therapeutic effect of glycyrrhizic acid compound ointment on imiquimod-induced psoriasis-like disease in mice.PloS one · 2023Article
- Patients with systemic sclerosis show phenotypic and functional defects in neutrophils.Allergy · 2022Article
- Soluble forms of cytokine and growth factor receptors: mechanisms of generation and modes of action in the regulation of local and systemic inflammation.FEBS letters · 2022Review
- Inhibition of CtBP-Regulated Proinflammatory Gene Transcription Attenuates Psoriatic Skin Inflammation.The Journal of investigative dermatology · 2022Article
- Selective Targeting of IL-15Rα Is Sufficient to Reduce Inflammation.Frontiers in immunology · 2022Article
- Interleukin-15 enhances proinflammatory T-cell responses in patients with MS and EAE.Neurology(R) neuroimmunology & neuroinflammation · 2021Article
- IL-15Rα-Independent IL-15 Signaling in Non-NK Cell-Derived IFNγ Driven Control ofFrontiers in immunology · 2021Article
- Cytokinocytes: the diverse contribution of keratinocytes to immune responses in skin.JCI insight · 2020Review
- The IL-15 / sIL-15Rα complex modulates immunity without effect on asthma features in mouse.Respiratory research · 2020Article
- Interleukin-15 (dys)regulation of lymphoid homeostasis: Implications for therapy of autoimmunity and cancer.The Journal of experimental medicine · 2020Review
- Dihydroartemisinin ameliorates psoriatic skin inflammation and its relapse by diminishing CD8Theranostics · 2020Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Stromal cells at epithelial surfaces contribute to innate immunity by sensing environmental danger signals and producing proinflammatory cytokines. However, the role of stromal cells in controlling local inflammation is unknown. We show that endogenous soluble IL-15 receptor α (IL-15Rα) derived from epidermal stroma, notably keratinocytes, protects against dendritic cell/IL-15-mediated, T cell-driven skin inflammation in vivo, and is relevant to human psoriasis. Selective lack of IL-15Rα on stromal epidermal cells exacerbated psoriasiform inflammation in animals. Epidermal IL-15Rα was shed by keratinocytes via proteolytic cleavage by matrix metalloproteinases upon stimulation with proinflammatory cytokines to counteract IL-15-induced proliferation of IL-17(+) αβ and γδ T cells and production of TNF, IL-23, IL-17, and IL-22 during skin inflammation. Notably, administration of soluble IL-15Rα was able to repress secretion of IL-1β, IL-6, and TNF by keratinocytes, dampen expansion of IL-17(+) αβ and γδ T cells in vivo, and prevent psoriasis in two mouse models, including human xenograft AGR mice. Serum levels of soluble IL-15Rα negatively correlated with disease severity, and levels rose upon successful treatment of psoriasis in patients. Thus, stressed epidermal stromal cells use soluble IL-15Rα to dampen chronic inflammatory skin disease.
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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.