{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T02:57:42Z","timestamp":1772852262160,"version":"3.50.1"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2019,6,1]],"date-time":"2019-06-01T00:00:00Z","timestamp":1559347200000},"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":[[2019,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Early life immune responses are deficient in Th1 lymphocytes that compromise neonatal vaccination. We found that IL-4 and IL-13 engage a developmentally expressed IL-4R\u03b1\/IL-13R\u03b11 heteroreceptor to endow IFN regulatory factor 1 (IRF-1) with apoptotic functions, which redirect murine neonatal Th1 reactivation to cell death. IL-4\/IL-13\u2013induced STAT6 phosphorylation serves to enhance IRF-1 transcription and promotes its egress from the nucleus. In the cytoplasm, IRF-1 can no longer serve as an anti-viral transcription factor but, instead, colocalizes with Bim and instigates the mitochondrial, or intrinsic, death pathway. The new pivotal function of IRF-1 in the death of neonatal Th1 cells stems from the ability of its gene to bind STAT6 for enhanced transcription and the proficiency of its protein to precipitate Bim-driven apoptosis. This cytokine-induced, IRF-1\u2013mediated developmental death network weakens neonatal Th1 responses during early life vaccination and increases susceptibility to viral infection.<\/jats:p>","DOI":"10.4049\/jimmunol.1800943","type":"journal-article","created":{"date-parts":[[2019,4,17]],"date-time":"2019-04-17T20:15:12Z","timestamp":1555532112000},"page":"3173-3186","source":"Crossref","is-referenced-by-count":4,"title":["A New IRF-1\u2013Driven Apoptotic Pathway Triggered by IL-4\/IL-13 Kills Neonatal Th1 Cells and Weakens Protection against Viral Infection"],"prefix":"10.1093","volume":"202","author":[{"given":"Mindy M","family":"Miller","sequence":"first","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine , Columbia MO 65212"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Subhasis","family":"Barik","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine , Columbia MO 65212"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexis N","family":"Cattin-Roy","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine , Columbia MO 65212"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tobechukwu K","family":"Ukah","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine , Columbia MO 65212"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine M","family":"Hoeman","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine , Columbia MO 65212"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4653-0050","authenticated-orcid":false,"given":"Habib","family":"Zaghouani","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine , Columbia MO 65212"},{"name":"Department of Child Health, University of Missouri School of Medicine , Columbia MO 65212"},{"name":"Department of Neurology, University of Missouri School of Medicine , Columbia MO 65212"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,6,1]]},"reference":[{"key":"2025030417562331200_r1","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/172603a0","article-title":"Actively acquired tolerance of foreign cells","volume":"172","author":"Billingham","year":"1953","journal-title":"Nature"},{"key":"2025030417562331200_r2","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1002\/eji.1830190223","article-title":"Resistance to experimental autoimmune encephalomyelitis induced by neonatal tolerization to myelin basic protein: clonal elimination vs. regulation of autoaggressive lymphocytes","volume":"19","author":"Qin","year":"1989","journal-title":"Eur. 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