{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T04:53:01Z","timestamp":1789966381847,"version":"4.0.1"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2012,4,1]],"date-time":"2012-04-01T00:00:00Z","timestamp":1333238400000},"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":[[2012,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The activity of IDO that catalyzes the degradation of tryptophan (Trp) into kynurenine (Kyn) increases after diseases caused by different infectious agents. Previously, we demonstrated that IDO has an important immunomodulatory function in immune-related diseases. However, the pathophysiological role of IDO following acute viral infection is not fully understood. To investigate the role of IDO in the l-Trp\u2013Kyn pathway during acute viral myocarditis, mice were infected with encephalomyocarditis virus, which induces acute myocarditis. We used IDO-deficient (IDO\u2212\/\u2212) mice and mice treated with 1-methyl-d,l-Trp (1-MT), an inhibitor of IDO, to study the importance of Trp\u2013Kyn pathway metabolites. Postinfection with encephalomyocarditis virus infection, the serum levels of Kyn increased, whereas those of Trp decreased, and IDO activity increased in the spleen and heart. The survival rate of IDO\u2212\/\u2212 or 1-MT\u2013treated mice was significantly greater than that of IDO+\/+ mice. Indeed, the viral load was suppressed in the IDO\u2212\/\u2212 or 1-MT\u2013treated mice. Furthermore, the levels of type I IFNs in IDO\u2212\/\u2212 mice and IDO\u2212\/\u2212 bone marrow-transplanted IDO+\/+ mice were significantly higher than those in IDO+\/+ mice, and treatment of IDO\u2212\/\u2212 mice with Kyn metabolites eliminated the effects of IDO\u2212\/\u2212 on the improved survival rates. These results suggest that IDO has an important role in acute viral myocarditis. Specifically, IDO increases the accumulation of Kyn pathway metabolites, which suppress type I IFNs production and enhance viral replication. We concluded that inhibition of the Trp\u2013Kyn pathway ameliorates acute viral myocarditis.<\/jats:p>","DOI":"10.4049\/jimmunol.1100997","type":"journal-article","created":{"date-parts":[[2012,3,15]],"date-time":"2012-03-15T07:33:41Z","timestamp":1331796821000},"page":"3980-3987","source":"Crossref","is-referenced-by-count":49,"title":["<scp>l<\/scp>-Tryptophan\u2013Kynurenine Pathway Metabolites Regulate Type I IFNs of Acute Viral Myocarditis in Mice"],"prefix":"10.1093","volume":"188","author":[{"given":"Masato","family":"Hoshi","sequence":"first","affiliation":[{"name":"Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine , Gifu 501-1194 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keishi","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Human Health Sciences, Kyoto University Graduate School of Medicine and Faculty of Medicine , Kyoto 606-8507 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyasu","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine , Gifu 501-1194 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirofumi","family":"Ohtaki","sequence":"additional","affiliation":[{"name":"Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine , Gifu 501-1194 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Arioka","sequence":"additional","affiliation":[{"name":"Human Health Sciences, Kyoto University Graduate School of Medicine and Faculty of Medicine , Kyoto 606-8507 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosuke","family":"Osawa","sequence":"additional","affiliation":[{"name":"Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine , Gifu 501-1194 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuko","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Human Health Sciences, Kyoto University Graduate School of Medicine and Faculty of Medicine , Kyoto 606-8507 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidetoshi","family":"Matsunami","sequence":"additional","affiliation":[{"name":"Department of Medicine, Matsunami General Hospital , Kasamatsu Cho, Gifu 501-6062 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Hara","sequence":"additional","affiliation":[{"name":"Department of Tumor Pathology, Gifu University Graduate School of Medicine , Gifu 501-1194 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuru","family":"Seishima","sequence":"additional","affiliation":[{"name":"Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine , Gifu 501-1194 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuniaki","family":"Saito","sequence":"additional","affiliation":[{"name":"Human Health Sciences, Kyoto University Graduate School of Medicine and Faculty of Medicine , Kyoto 606-8507 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,4,15]]},"reference":[{"key":"2025032410025513400_r1","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.leukres.2008.05.023","article-title":"Indoleamine 2,3-dioxygenase is highly expressed in human adult T-cell leukemia\/lymphoma and chemotherapy changes tryptophan catabolism in serum and reduced activity","volume":"33","author":"Hoshi","year":"2009","journal-title":"Leuk. 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