{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T05:13:20Z","timestamp":1772255600542,"version":"3.50.1"},"reference-count":92,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2017,4,1]],"date-time":"2017-04-01T00:00:00Z","timestamp":1491004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Toxic shock syndrome (TSS) is caused by staphylococcal and streptococcal superantigens (SAgs) that provoke a swift hyperinflammatory response typified by a cytokine storm. The precipitous decline in the host\u2019s clinical status and the lack of targeted therapies for TSS emphasize the need to identify key players of the storm\u2019s initial wave. Using a humanized mouse model of TSS and human cells, we herein demonstrate that SAgs elicit in vitro and in vivo IL-17A responses within hours. SAg-triggered human IL-17A production was characterized by remarkably high mRNA stability for this cytokine. A distinct subpopulation of CD4+ effector memory T (TEM) cells that secrete IL-17A, but not IFN-\u03b3, was responsible for early IL-17A production. We found mouse \u201cTEM-17\u201d cells to be enriched within the intestinal epithelium and among lamina propria lymphocytes. Furthermore, interfering with IL-17A receptor signaling in human PBMCs attenuated the expression of numerous inflammatory mediators implicated in the TSS-associated cytokine storm. IL-17A receptor blockade also abrogated the secondary effect of SAg-stimulated PBMCs on human dermal fibroblasts as judged by C\/EBP \u03b4 expression. Finally, the early IL-17A response to SAgs was pathogenic because in vivo neutralization of IL-17A in humanized mice ameliorated hepatic and intestinal damage and reduced mortality. Together, our findings identify CD4+ TEM cells as a key effector of TSS and reveal a novel role for IL-17A in TSS immunopathogenesis. Our work thus elucidates a pathogenic, as opposed to protective, role for IL-17A during Gram-positive bacterial infections. Accordingly, the IL-17\u2013IL-17R axis may provide an attractive target for the management of SAg-mediated illnesses.<\/jats:p>","DOI":"10.4049\/jimmunol.1601366","type":"journal-article","created":{"date-parts":[[2017,11,9]],"date-time":"2017-11-09T09:41:44Z","timestamp":1510220504000},"page":"2805-2818","source":"Crossref","is-referenced-by-count":38,"title":["Rapid and Rigorous IL-17A Production by a Distinct Subpopulation of Effector Memory T Lymphocytes Constitutes a Novel Mechanism of Toxic Shock Syndrome Immunopathology"],"prefix":"10.1093","volume":"198","author":[{"given":"Peter A","family":"Szabo","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Western University , London, Ontario N6A 5C1,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ankur","family":"Goswami","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Western University , London, Ontario N6A 5C1,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Delfina M","family":"Mazzuca","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Western University , London, Ontario N6A 5C1,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyoungok","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Western University , London, Ontario N6A 5C1,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6195-2644","authenticated-orcid":false,"given":"David B","family":"O\u2019Gorman","sequence":"additional","affiliation":[{"name":"Cell and Molecular Biology Laboratory, Roth | McFarlane Hand and Upper Limb Centre, Western University , London, Ontario N6A 4V2,","place":["Canada"]},{"name":"Department of Biochemistry, Western University , London, Ontario N6A 5C1,","place":["Canada"]},{"name":"Lawson Health Research Institute , London, Ontario N6C 2R5,","place":["Canada"]},{"name":"Department of Surgery, Western University , London, Ontario N6A 4V2,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A","family":"Hess","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Western University , London, Ontario N6A 5C1,","place":["Canada"]},{"name":"Krembil Centre for Stem Cell Biology, Molecular Medicine Research Group, Robarts Research Institute , London, Ontario N6A 5B7,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian D","family":"Welch","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of British Columbia , Vancouver, British Columbia V6T 2B5,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3118-5111","authenticated-orcid":false,"given":"Howard A","family":"Young","sequence":"additional","affiliation":[{"name":"Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute-Frederick , Frederick, MD 21702"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9792-8694","authenticated-orcid":false,"given":"Bhagirath","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Western University , London, Ontario N6A 5C1,","place":["Canada"]},{"name":"Lawson Health Research Institute , London, Ontario N6C 2R5,","place":["Canada"]},{"name":"Centre for Human Immunology, Western University , London, Ontario N6A 5C1,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3742-7289","authenticated-orcid":false,"given":"John K","family":"McCormick","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Western University , London, Ontario N6A 5C1,","place":["Canada"]},{"name":"Lawson Health Research Institute , London, Ontario N6C 2R5,","place":["Canada"]},{"name":"Centre for Human Immunology, Western University , London, Ontario N6A 5C1,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1125-8176","authenticated-orcid":false,"given":"S M Mansour","family":"Haeryfar","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Western University , London, Ontario N6A 5C1,","place":["Canada"]},{"name":"Lawson Health Research Institute , London, Ontario N6C 2R5,","place":["Canada"]},{"name":"Centre for Human 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