{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T04:48:18Z","timestamp":1784954898157,"version":"3.55.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2012,8,1]],"date-time":"2012-08-01T00:00:00Z","timestamp":1343779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Science, Sports and Culture","doi-asserted-by":"crossref","award":["12670621"],"award-info":[{"award-number":["12670621"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Science, Sports and Culture","doi-asserted-by":"crossref","award":["14021121"],"award-info":[{"award-number":["14021121"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Science, Sports and Culture","doi-asserted-by":"crossref","award":["22790945"],"award-info":[{"award-number":["22790945"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Science, Sports and Culture","doi-asserted-by":"crossref","award":["21790963"],"award-info":[{"award-number":["21790963"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Research on Health Sciences Focusing on Drug Innovation"},{"DOI":"10.13039\/100007416","name":"Japan Health Sciences Foundation","doi-asserted-by":"publisher","award":["KH51052"],"award-info":[{"award-number":["KH51052"]}],"id":[{"id":"10.13039\/100007416","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Japan Rheumatism Foundation"},{"name":"Toho University Graduate School of Medicine","award":["10-02"],"award-info":[{"award-number":["10-02"]}]},{"name":"Toho University Graduate School of Medicine","award":["08-02"],"award-info":[{"award-number":["08-02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>CCR7 ligands activate PI3-kinase and NF-\u03baB pathways in DC to induce the expression of IL-23p19.<\/jats:p>\n               <jats:p>We reported previously that the production of IL-23 is impaired in DCs from mice that lack expression of the chemokines CCL19 and CCL21, which share the receptor CCR7, suggesting that these chemokines are required for IL-23 expression. However, the molecular mechanism of CCR7-mediated IL-23 production in DCs is unknown. We found that CCL19 and CCL21 stimulated DCs through CCR7 and induced transcription of IL-23p19 mRNA and IL-23 production in splenic and BMDC. Stimulation of DCs with CCR7 ligands induced phosphorylation of MAPK family members and of Akt, but only a specific PI3K inhibitor, LY294002, not inhibitors of ERK, JNK, or p38, decreased IL-23p19 transcription and IL-23 production. In DCs stimulated with CCL19 or CCL21, I\u03baB\u03b1 was degraded, and NF-\u03baB was translocated into the nucleus. Prevention of NF-\u03baB activation blocked chemokine-mediated IL-23p19 transcription. A PI3K inhibitor abolished NF-\u03baB activation and IL-23 production. Based on these findings, we concluded that PI3K and NF-\u03baB signaling pathways play a critical role in CCR7-mediated IL-23 production in murine DCs. As IL-23 contributes to Th17 cell generation, and Th17 cells are pathogenic in autoimmune diseases, precise elucidation of these mechanisms would contribute to the development of strategies to control autoimmune diseases.<\/jats:p>","DOI":"10.1189\/jlb.0811415","type":"journal-article","created":{"date-parts":[[2012,5,17]],"date-time":"2012-05-17T17:07:25Z","timestamp":1337274445000},"page":"309-318","source":"Crossref","is-referenced-by-count":32,"title":["CCR7 ligands up-regulate IL-23 through PI3-kinase and NF-\u03baB pathway in dendritic cells"],"prefix":"10.1093","volume":"92","author":[{"given":"Taku","family":"Kuwabara","sequence":"first","affiliation":[{"name":"Departments of Immunology, Toho University School of Medicine , Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuriko","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Departments of Immunology, Toho University School of Medicine , Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumio","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Departments of Immunology, Toho University School of Medicine , Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motonari","family":"Kondo","sequence":"additional","affiliation":[{"name":"Departments of Immunology, Toho University School of Medicine , Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Sekiya","sequence":"additional","affiliation":[{"name":"Oral Surgery, Toho University School of Medicine , Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terutaka","family":"Kakiuchi","sequence":"additional","affiliation":[{"name":"Departments of Immunology, Toho University School of Medicine , Tokyo, Japan"},{"name":"Advanced Medical Research Center, Toho University School of Medicine , Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,8,1]]},"reference":[{"key":"2023012312544124700_B1","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1146\/annurev.immunol.15.1.675","article-title":"Human chemokines: an update","volume":"15","author":"Baggiolini","year":"1997","journal-title":"Annu. 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