{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T12:55:38Z","timestamp":1789908938820,"version":"4.0.1"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2007,6,1]],"date-time":"2007-06-01T00:00:00Z","timestamp":1180656000000},"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":[[2007,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Protection against Leishmania major in resistant C57BL\/6 mice is mediated by Th1 cells, whereas susceptibility in BALB\/c mice is the result of Th2 development. IL-12 release by L. major-infected dendritic cells (DC) is critically involved in differentiation of Th1 cells. Previously, we reported that strain differences in the production of DC-derived factors, e.g., IL-1\u03b1\u03b2, are in part responsible for disparate disease outcome. In the present study, we analyzed the release of IL-12 from DC in more detail. Stimulated DC from C57BL\/6 and BALB\/c mice released comparable amounts of IL-12p40 and p70. In the absence of IL-4, BALB\/c DC produced significantly more IL-12p40 than C57BL\/6 DC. Detailed analyses by Western blot and ELISA revealed that one-tenth of IL-12p40 detected in DC supernatants was released as the IL-12 antagonist IL-12p40 homodimer (IL-12p80). BALB\/c DC released \u223c2-fold more IL-12p80 than C57BL\/6 DC both in vitro and in vivo. Local injection of IL-12p80 during the first 3 days after infection resulted in increased lesion volumes for several weeks in both L. major-infected BALB\/c or C57BL\/6 mice, in higher lesional parasite burdens, and decreased Th1-cytokine production. Finally, IL-12p40-transgenic C57BL\/6 mice characterized by overexpression of p40 showed increased levels of serum IL-12p80 and enhanced disease susceptibility. Thus, in addition to IL-1\u03b1\u03b2, strain-dependent differences in the release of other DC-derived factors such as IL-12p80 may influence genetically determined disease outcome.<\/jats:p>","DOI":"10.4049\/jimmunol.178.11.7251","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T23:24:11Z","timestamp":1397863451000},"page":"7251-7258","source":"Crossref","is-referenced-by-count":32,"title":["Dendritic Cell-Derived IL-12p40 Homodimer Contributes to Susceptibility in Cutaneous Leishmaniasis in BALB\/c Mice"],"prefix":"10.1093","volume":"178","author":[{"given":"Axel P","family":"Nigg","sequence":"first","affiliation":[{"name":"Department of Dermatology, Johannes Gutenberg-University , Mainz ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Zahn","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Johannes Gutenberg-University , Mainz ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik","family":"Ru\u0308ckerl","sequence":"additional","affiliation":[{"name":"Forschungszentrum Borstel ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Ho\u0308lscher","sequence":"additional","affiliation":[{"name":"Forschungszentrum Borstel ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Yoshimoto","sequence":"additional","affiliation":[{"name":"Intractable Immune System Disease Research Center, Tokyo Medical University , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan M","family":"Ehrchen","sequence":"additional","affiliation":[{"name":"Department of Dermatology , Mu\u0308nster ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Wo\u0308lbing","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Johannes Gutenberg-University , Mainz ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark C","family":"Udey","sequence":"additional","affiliation":[{"name":"Dermatology Branch, National Cancer Institute, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"von Stebut","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Johannes Gutenberg-University , Mainz ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2007,6,1]]},"reference":[{"key":"2025032702494063100_R1","first-page":"845","volume-title":"Nat. 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