{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T15:12:36Z","timestamp":1777648356284,"version":"3.51.4"},"reference-count":59,"publisher":"Rockefeller University Press","issue":"7","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1999,10,4]]},"abstract":"<jats:p>In vivo manipulation of cytokine and\/or cytokine receptor expression has previously shown that resistance to infection with the caecum-dwelling helminth Trichuris muris is dependent on interleukin (IL)-4 and IL-13 while susceptibility is associated with a T helper cell type 1 (Th1) cytokine response. Using gene-targeted mice deficient in tumor necrosis factor (TNF) receptor signaling and anti\u2013TNF-\u03b1 monoclonal antibody treatment, we have extended these studies to reveal a critical role for TNF-\u03b1 in regulation of Th2 cytokine\u2013mediated host protection. In vivo blockade of TNF-\u03b1 in normally resistant mice, although not altering IL-4, IL-5, or IL-13 production in the draining lymph node, significantly delayed worm expulsion for the duration of treatment. IL-13\u2013mediated worm expulsion in IL-4 knockout (KO) mice was also shown to be TNF-\u03b1 dependent, and could be enhanced by administration of recombinant TNF-\u03b1. Furthermore, TNF receptor KO mice failed to expel T. muris, producing high levels of parasite-specific immunoglobulin G2a and the generation of a predominantly Th1 response, suggesting that the absence of TNF function from the onset of infection dramatically alters the phenotype of the response. These results provide the first demonstration of the role of TNF-\u03b1 in regulating Th2 cytokine\u2013mediated responses at mucosal sites, and have implications for the design of rational therapies against helminth infection and allergy.<\/jats:p>","DOI":"10.1084\/jem.190.7.953","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:48:54Z","timestamp":1027702134000},"page":"953-962","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":117,"title":["Tumor Necrosis Factor \u03b1 Is a Critical Component of Interleukin 13\u2013Mediated Protective T Helper Cell Type 2 Responses during Helminth Infection"],"prefix":"10.1084","volume":"190","author":[{"given":"David","family":"Artis","sequence":"first","affiliation":[{"name":"aImmunology Group, School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom"},{"name":"cCancer Research Campaign (CRC) Department of Epithelial Biology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester M20 9BX, United Kingdom"}]},{"given":"Neil E.","family":"Humphreys","sequence":"additional","affiliation":[{"name":"aImmunology Group, School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom"}]},{"given":"Allison J.","family":"Bancroft","sequence":"additional","affiliation":[{"name":"aImmunology Group, School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom"}]},{"given":"Nancy J.","family":"Rothwell","sequence":"additional","affiliation":[{"name":"bInstitute of Neuroscience, School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom"}]},{"given":"Christopher S.","family":"Potten","sequence":"additional","affiliation":[{"name":"cCancer Research Campaign (CRC) Department of Epithelial Biology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester M20 9BX, United Kingdom"}]},{"given":"Richard K.","family":"Grencis","sequence":"additional","affiliation":[{"name":"aImmunology Group, School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom"}]}],"member":"291","published-online":{"date-parts":[[1999,10,4]]},"reference":[{"key":"2023072509000517300_R1","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/383787a0","article-title":"Functional diversity of helper T lymphocytes","volume":"383","author":"Abbas","year":"1996","journal-title":"Nature."},{"key":"2023072509000517300_R2","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/0167-5699(96)80606-2","article-title":"The expanding universe of T-cell subsetsTh1, Th2 and more","volume":"17","author":"Mosmann","year":"1996","journal-title":"Immunol. 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