{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T10:58:17Z","timestamp":1790506697243,"version":"4.1.0"},"reference-count":88,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>IL-33 is a multifunctional cytokine that mediates local inflammation upon tissue damage. IL-33 is known to act on multiple cell types including group 2 innate lymphoid cells (ILC2s), Th2 cells, and mast cells to drive production of Th2 cytokines including IL-5 and IL-13. IL-33 signaling activity through transmembrane ST2L can be inhibited by soluble ST2 (sST2), which acts as a decoy receptor. Previous findings suggested that modulation of IL-13 levels in mice lacking decoy IL-13R\u03b12, or mice lacking IL-13, impacted responsiveness to IL-33. In this study, we used Il13\u2212\/\u2212 mice to investigate whether IL-13 regulates IL-33 activity by modulating the transmembrane and soluble forms of ST2. In Il13\u2212\/\u2212 mice, the effects of IL-33 administration were exacerbated relative to wild type (WT). Il13\u2212\/\u2212 mice administered IL-33 i.p. had heightened splenomegaly, more immune cells in the peritoneum including an expanded ST2L+ ILC2 population, increased eosinophilia in the spleen and peritoneum, and reduced sST2 in the circulation and peritoneum. In the spleen, lung, and liver of mice given IL-33, gene expression of both isoforms of ST2 was increased in Il13\u2212\/\u2212 mice relative to WT. We confirmed fibroblasts to be an IL-13-responsive cell type that can regulate IL-33 activity through production of sST2. This study elucidates the important regulatory activity that IL-13 exerts on IL-33 through induction of IL-33 decoy receptor sST2 and through modulation of ST2L+ ILC2s.<\/jats:p>","DOI":"10.4049\/jimmunol.2100655","type":"journal-article","created":{"date-parts":[[2021,11,17]],"date-time":"2021-11-17T18:45:17Z","timestamp":1637174717000},"page":"3070-3080","source":"Crossref","is-referenced-by-count":18,"title":["IL-13 Controls IL-33 Activity through Modulation of ST2"],"prefix":"10.1093","volume":"207","author":[{"given":"Melvin","family":"Zhang","sequence":"first","affiliation":[{"name":"Inflammation and Immunology Research Unit, Pfizer, Inc. , Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L","family":"Duffen","sequence":"additional","affiliation":[{"name":"Inflammation and Immunology Research Unit, Pfizer, Inc. , Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl H","family":"Nocka","sequence":"additional","affiliation":[{"name":"Inflammation and Immunology Research Unit, Pfizer, Inc. , Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6048-3732","authenticated-orcid":false,"given":"Marion T","family":"Kasaian","sequence":"additional","affiliation":[{"name":"Inflammation and Immunology Research Unit, Pfizer, Inc. , Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,12,15]]},"reference":[{"key":"2025022610324331600_r1","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1111\/imr.12619","article-title":"Interleukin-33 (IL-33): a nuclear cytokine from the IL-1 family","volume":"281","author":"Cayrol","year":"2018","journal-title":"Immunol. 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