{
  "abstract": "Manqiu Jin,1,2 Qianwen Li,1,2 Magda Babina1,2 1Institute of Allergology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, 12203, Germany; 2Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Immunology and Allergology IA, Berlin, 12203, GermanyCorrespondence: Magda Babina, Institute of Allergology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, 12203, Germany, Email magda.babina@charite.deAbstract: Interleukin-33 (IL-33), a member of the IL-1 cytokine family, exists in both full-length and mature forms, and acts as a nuclear alarmin and an extracellular cytokine, respectively. Upon skin damage or pathogenic insults, IL-33 is released from structural cells, activating innate and type 2 immune responses. Mast cells (MCs), which express high levels of the IL-33 receptor ST2, are key effectors in this axis. IL-33 regulates MC survival, proliferation, phenotype, and function, modulating receptor expression, granule mediators, and cytokines. While acute IL-33 exposure primes MCs for pro-inflammatory responses and synergizes with other stimuli to amplify degranulation and cytokine release, prolonged exposure induces a hypo-responsive phenotype characterized by downregulation of FcϵRI and MRGPRX2, reduced MC degranulation and cytokine profile shifting toward tolerance. The IL-33/MC axis has been implicated in the pathogenesis of skin diseases like atopic dermatitis (AD), allergic contact dermatitis, psoriasis, and urticaria.Genetic studies link IL-33/ST2 polymorphisms to disease susceptibility, while elevated IL-33 levels can correlate with disease severity. Despite promising preclinical data, trials targeting the IL-33/ST2 pathway have yielded mixed and rather disappointing results, perhaps due to IL-33’s dual role in both promoting and resolving inflammation. This may reflect chronic exposure-induced MC hyporesponsiveness, sST2-mediated negative feedback, and the involvement of IL-33 in tissue repair. Differences in IL-33-induced signaling between primary human skin MCs and rodent MC models further highlight the challenges of translating preclinical findings into clinical applications. In this review, we comprehensively examine the molecular mechanisms and disease implications of IL-33 and the IL-33/MC connection in cutaneous health and disease.Keywords: signaling, cytokines, atopic dermatitis, allergic contact dermatitis, psoriasis, urticaria",
  "abstract_shown": true,
  "affiliations": [
    "Institute of Allergology"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jin M"
    },
    {
      "affs": [
        0
      ],
      "name": "Li Q"
    },
    {
      "name": "Babina M"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5t5397w44me25.bib",
  "cited_by": 0,
  "doi": null,
  "fulltext_url": "https://www.dovepress.com/il-33-and-mast-cells-in-the-skin-from-molecular-mechanisms-to-disease--peer-reviewed-fulltext-article-JIR",
  "id": "5t5397w44me25",
  "issns": [
    "1178-7031"
  ],
  "landing_url": "https://www.dovepress.com/il-33-and-mast-cells-in-the-skin-from-molecular-mechanisms-to-disease--peer-reviewed-fulltext-article-JIR",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RB1-214"
    ],
    [
      "lcc",
      "RM1-950"
    ]
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  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-08",
  "publisher": "Dove Medical Press",
  "ris": "https://research.draconitic.com/paper/5t5397w44me25.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T14:21:26Z",
      "native_id": "064c4c6db12d4d89bbb6a75697258977",
      "source": "doaj",
      "url": "https://www.dovepress.com/il-33-and-mast-cells-in-the-skin-from-molecular-mechanisms-to-disease--peer-reviewed-fulltext-article-JIR"
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  "subjects": [
    {
      "field": "medicine",
      "origin": "lcc:RM1-950",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "IL-33 and Mast Cells in the Skin: From Molecular Mechanisms to Disease Implications",
  "title_text": "IL-33 and Mast Cells in the Skin: From Molecular Mechanisms to Disease Implications",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T14:21:26Z",
  "url": "https://research.draconitic.com/paper/5t5397w44me25",
  "venue": "Journal of Inflammation Research",
  "versions": []
}