{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T23:32:46Z","timestamp":1768347166495,"version":"3.49.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2021,11,12]],"date-time":"2021-11-12T00:00:00Z","timestamp":1636675200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"},{"start":{"date-parts":[[2021,11,12]],"date-time":"2021-11-12T00:00:00Z","timestamp":1636675200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2021,11,12]],"date-time":"2021-11-12T00:00:00Z","timestamp":1636675200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,7,23]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cytokines play critical roles in regulating iNKT cell development, activation, and maturation. TNF-\u03b1 co-occurs with iNKT cells in steady-state and many disease conditions. How TNF-\u03b1 affects iNKT cell function has not been thoroughly investigated. It was found that chronic alcohol consumption enhanced iNKT cell activation and maturation. The underlying mechanism is not known. Herein, a TNF-\u03b1 KO mouse model was used to address these issues. It was found that the depletion of TNF-\u03b1 mitigated alcohol consumption-enhanced iNKT cell activation and maturation. In steady-state, depletion of TNF-\u03b1 did not affect the frequency of iNKT cells in the thymus and spleen but decreased iNKT cells in the liver and increased liver iNKT cell apoptosis. The portion of stage-2 immature iNKT cells increased, stage-3 mature iNKT cells decreased in the thymus of TNF-\u03b1 KO mice, suggesting that depletion of TNF-\u03b1 impairs iNKT cell development and maturation. The percentage of CD69+ iNKT cells was significantly lower in the thymus, spleen, and liver of TNF-\u03b1 KO mice compared to their wild-type littermates, suggesting that depletion of TNF-\u03b1 inhibits iNKT cell activation. Moreover, the percentage of splenic IL-4- and IFN-\u03b3-producing iNKT cells was significantly lower in TNF-\u03b1 KO mice than in their wild-type littermates. The depletion of TNF-\u03b1 increased PLZF+ iNKT cells in the thymus and down-regulated the expression of CD122 on iNKT cells. Collectively, these results support that TNF-\u03b1 plays a vital role in the regulation of iNKT cell development, activation, and maturation, and alcohol consumption enhances iNKT cell activation and maturation through TNF-\u03b1.<\/jats:p>","DOI":"10.1002\/jlb.1a0821-466r","type":"journal-article","created":{"date-parts":[[2021,11,12]],"date-time":"2021-11-12T09:29:07Z","timestamp":1636709347000},"page":"233-241","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Effects of TNF-\u03b1 deletion on iNKT cell development, activation, and maturation in the steady-state and chronic alcohol-consuming mice"],"prefix":"10.1093","volume":"112","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6620-7173","authenticated-orcid":false,"given":"Hui","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University , Spokane, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Faya","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University , Spokane, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samantha","family":"Modrak","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University , Spokane, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,11,12]]},"reference":[{"key":"2023032107585184100_","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1172\/JCI200423594","article-title":"Going both ways: immune regulation via CD1d-dependent NKT cells","volume":"114","author":"Godfrey","year":"2004","journal-title":"J Clin Invest"},{"key":"2023032107585184100_","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1158\/2326-6066.CIR-15-0062","article-title":"The regulatory role of invariant NKT cells in tumor immunity","volume":"3","author":"McEwen-Smith","year":"2015","journal-title":"Cancer Immunol Res"},{"key":"2023032107585184100_","doi-asserted-by":"crossref","first-page":"5582","DOI":"10.4049\/jimmunol.1501092","article-title":"Structural and Functional Changes of the Invariant NKT Clonal Repertoire in Early Rheumatoid Arthritis","volume":"195","author":"Mansour","year":"2015","journal-title":"J.Immunol"},{"key":"2023032107585184100_","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1189\/JLB.0309135","article-title":"Liver natural killer and natural killer T cells: immunobiology and emerging roles in liver diseases","volume":"86","author":"Gao","year":"2009","journal-title":"J. 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