{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T23:29:43Z","timestamp":1793316583021,"version":"4.5.0"},"reference-count":69,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:00:00Z","timestamp":1756080000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Texas Medical Branch Institute for Human Infection and Immunity"},{"name":"McLaughlin Fund, the Sealy Foundation at the University of Texas Medical Branch","award":["R01AI135061"],"award-info":[{"award-number":["R01AI135061"]}]},{"name":"McLaughlin Fund, the Sealy Foundation at the University of Texas Medical Branch","award":["R01AI166668"],"award-info":[{"award-number":["R01AI166668"]}]},{"name":"McLaughlin Fund, the Sealy Foundation at the University of Texas Medical Branch","award":["1R01AI153602"],"award-info":[{"award-number":["1R01AI153602"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,8,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The pathology of severe COVID-19 is due to a hyperinflammatory immune response persisting after viral clearance. To understand how the immune response to SARS-CoV-2 is regulated to avoid severe COVID-19, we tested relevant immunoregulatory cytokines. Transforming growth factor \u03b2 (TGF-\u03b2), interleukin (IL)-10, and IL-4 were neutralized upon infection with mouse-adapted SARS-CoV-2 (CMA3p20), a model of mild disease; lung inflammation was quantified by histology and flow cytometry at early and late time points. Mild weight loss and lung inflammation including consolidation and alveolar thickening were evident 3\u2009d postinfection (dpi), and inflammation persisted to 7\u2009dpi. Coinciding with early monocytic infiltrates, CCL2 and granulocyte colony-stimulating factor were transiently produced 3\u2009dpi, while IL-12 and CCL5 persisted to 7\u2009dpi, modeling viral and inflammatory phases of disease. Neutralization of TGF-\u03b2, but not IL-10 or IL-4, significantly increased lung inflammatory monocytes and elevated serum but not lung IL-6. Neutralization of IL-4 prolonged weight loss and increased early perivascular infiltration without changing viral titer. Anti-IL-4 reduced expression of Arg1, a gene associated with alternative activation of macrophages. Neutralizing TGF-\u03b2 and IL-4 had differential effects on pathology after virus control. Lung perivascular infiltration was reduced 7\u2009dpi by neutralization of IL-4 or TGF-\u03b2, and periairway inflammation was affected by anti-TGF-\u03b2, while alveolar infiltrates were not affected by either. Anti-IL-4 prolonged IL-12 to 7\u2009dpi along with reduced IL-10 in lungs. Overall, the immunoregulatory cytokines TGF-\u03b2 and IL-4 dampen initial inflammation in this mouse-adapted SARS-CoV-2 infection, suggesting that promotion of immunoregulation could help patients in early stages of disease.<\/jats:p>","DOI":"10.1093\/immhor\/vlaf032","type":"journal-article","created":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T23:49:58Z","timestamp":1756165798000},"source":"Crossref","is-referenced-by-count":2,"title":["IL-4 and TGF-\u03b2 regulate inflammatory cytokines and cellular infiltration in the lung and systemic IL-6 in mouse-adapted SARS-CoV-2 infection"],"prefix":"10.1093","volume":"9","author":[{"given":"Solomon","family":"Taye Sima","sequence":"first","affiliation":[{"name":"Center for Immunity and Inflammation, New Jersey Medical School, Rutgers Health , Newark, NJ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucinda","family":"Puebla-Clark","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, University of Texas Medical Branch , Galveston, TX,","place":["United States"]},{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch , Galveston, TX,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Gonzalez-Orozco","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch , Galveston, TX,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark Joseph","family":"Endrino","sequence":"additional","affiliation":[{"name":"Center for Immunity and Inflammation, New Jersey Medical School, Rutgers Health , Newark, NJ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas R","family":"Shelite","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, University of Texas Medical Branch , Galveston, TX,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiang-Chi","family":"Tseng","sequence":"additional","affiliation":[{"name":"Center for Virus-Host-Innate Immunity and Department of Medicine, New Jersey Medical School, Rutgers Health , Newark, NJ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yazmin B","family":"Martinez-Martinez","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch , Galveston, TX,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew B","family":"Huante","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch , Galveston, TX,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah G","family":"Federman","sequence":"additional","affiliation":[{"name":"Center for Immunity and Inflammation, New Jersey Medical School, Rutgers Health , Newark, NJ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Komi","family":"Gbedande","sequence":"additional","affiliation":[{"name":"Center for Immunity and Inflammation, New Jersey Medical School, Rutgers Health , Newark, NJ,","place":["United States"]},{"name":"Division of Infectious Diseases, Department of Internal Medicine, University of Texas Medical Branch , Galveston, TX,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vineet D","family":"Menachery","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch , Galveston, TX,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark C","family":"Siracusa","sequence":"additional","affiliation":[{"name":"Center for Immunity and Inflammation, New Jersey Medical School, Rutgers Health , Newark, NJ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A","family":"Endsley","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch , Galveston, TX,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara M","family":"Dann","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, University of Texas Medical Branch , Galveston, TX,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janice J","family":"Endsley","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch , Galveston, TX,","place":["United 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