{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T05:04:51Z","timestamp":1770354291998,"version":"3.49.0"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2003,3,1]],"date-time":"2003-03-01T00:00:00Z","timestamp":1046476800000},"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":[[2003,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Th2 responses are clearly involved in the pathogenesis of atopic disease. Thus, understanding the factors responsible for Th2 sensitization at sites of allergen exposure, such as airway and skin, is crucial for directing therapeutic or preventive strategies. Contrary to other models of Th2 sensitization to proteins, we have reported that Th2 responses induced by epicutaneous exposure to OVA are IL-4 independent. Combined deficiency of both IL-4 and IL-13 signaling did prevent Th2 generation, suggesting that IL-13 was mediating these IL-4-independent responses. It was not clear, however, whether IL-13 was simply replacing the need for IL-4 in genetically deficient mice or if IL-13 played a unique role. In the present study, we show that Th2 responses induced by epicutaneous OVA exposure (including lung inflammatory responses after inhaled Ag challenge, OVA-specific IgG1, and draining lymph node IL-5 production) are impaired in IL-13-deficient (IL-13\u2212\/\u2212) mice compared with wild type. In contrast, i.p. sensitization of IL-13\u2212\/\u2212 mice resulted in responses equivalent to wild type. Generation of contact hypersensitivity to dinitrofluorobenzene, which involves Th1 and CD8+ effector cells, was also intact in IL-13\u2212\/\u2212 mice. Taken together, the data indicate that IL-13 is the major inducer of Th2 generation in the cutaneous microenvironment, being required independently of IL-4. This fact, in combination with the known abundance of IL-13 in atopic dermatitis skin lesions, emphasizes the potentially important role of the skin as a site for Th2 sensitization to environmental allergens, particularly in atopic individuals.<\/jats:p>","DOI":"10.4049\/jimmunol.170.5.2488","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T21:32:44Z","timestamp":1398029564000},"page":"2488-2495","source":"Crossref","is-referenced-by-count":83,"title":["IL-13 Is Necessary, Not Simply Sufficient, for Epicutaneously Induced Th2 Responses to Soluble Protein Antigen"],"prefix":"10.1093","volume":"170","author":[{"given":"Christina A","family":"Herrick","sequence":"first","affiliation":[{"name":"Department of Dermatology, Yale University School of Medicine , New Haven, CT 06520"},{"name":"Section of Immunobiology, Yale University School of Medicine , New Haven, CT 06520"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lan","family":"Xu","sequence":"additional","affiliation":[{"name":"Section of Immunobiology, Yale University School of Medicine , New Haven, CT 06520"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew N J","family":"McKenzie","sequence":"additional","affiliation":[{"name":"Medical Research Council Laboratory of Molecular Biology , Cambridge ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert E","family":"Tigelaar","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Yale University School of Medicine , New Haven, CT 06520"},{"name":"Section of Immunobiology, Yale University School of Medicine , New Haven, CT 06520"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kim","family":"Bottomly","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Yale University School of Medicine , New Haven, CT 06520"},{"name":"Section of Immunobiology, Yale University School of Medicine , New Haven, CT 06520"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2003,3,1]]},"reference":[{"key":"2026020210075485400_R1","first-page":"184","volume-title":"J. 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