{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T04:34:36Z","timestamp":1791174876980,"version":"4.1.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2014,1,13]],"date-time":"2014-01-13T00:00:00Z","timestamp":1389571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>IDO2 is implicated in tryptophan catabolism and immunity but its physiological functions are not well established. Here we report the characterization of mice genetically deficient in IDO2, which develop normally but exhibit defects in IDO-mediated T-cell regulation and inflammatory responses. Construction of this strain was prompted in part by our discovery that IDO2 function is attenuated in macrophages from Ido1\u2212\/\u2212 mice due to altered message splicing, generating a functional mosaic with implications for interpreting findings in Ido1\u2013\/\u2013 mice. No apparent defects were observed in Ido2\u2013\/\u2013 mice in embryonic development or hematopoietic differentiation, with wild-type profiles documented for kynurenine in blood serum and for immune cells in spleen, lymph nodes, peritoneum, thymus and bone marrow of naive mice. In contrast, upon immune stimulation we determined that IDO1-dependent T regulatory cell generation was defective in Ido2\u2212\/\u2212 mice, supporting Ido1\u2013Ido2 genetic interaction and establishing a functional role for Ido2 in immune modulation. Pathophysiologically, both Ido1\u2212\/\u2212 and Ido2\u2212\/\u2212 mice displayed reduced skin contact hypersensitivity responses, but mechanistic distinctions were apparent, with only Ido2 deficiency associated with a suppression of immune regulatory cytokines that included GM-CSF, G-CSF, IFN-\u03b3, TNF-\u03b1, IL-6 and MCP-1\/CCL2. Different contributions to inflammation were likewise indicated by the finding that Ido2\u2212\/\u2212 mice did not phenocopy Ido1\u2212\/\u2212 mice in the reduced susceptibility of the latter to inflammatory skin cancer. Taken together, our results offer an initial glimpse into immune modulation by IDO2, revealing its genetic interaction with IDO1 and distinguishing its non-redundant contributions to inflammation.<\/jats:p>","DOI":"10.1093\/intimm\/dxt073","type":"journal-article","created":{"date-parts":[[2014,1,9]],"date-time":"2014-01-09T06:05:25Z","timestamp":1389247525000},"page":"357-367","source":"Crossref","is-referenced-by-count":180,"title":["IDO2 is critical for IDO1-mediated T-cell regulation and exerts a non-redundant function in inflammation"],"prefix":"10.1093","volume":"26","author":[{"given":"Richard","family":"Metz","sequence":"first","affiliation":[{"name":"New Link Genetics Corporation 1 , Ames, IA 50010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney","family":"Smith","sequence":"additional","affiliation":[{"name":"Lankenau Institute for Medical Research 2 , Wynnewood, PA 19096 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James B.","family":"DuHadaway","sequence":"additional","affiliation":[{"name":"Lankenau Institute for Medical Research 2 , Wynnewood, PA 19096 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip","family":"Chandler","sequence":"additional","affiliation":[{"name":"Immunotherapy Center, Georgia Regents University 3 , Augusta, GA 30912 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Babak","family":"Baban","sequence":"additional","affiliation":[{"name":"Immunotherapy Center, Georgia Regents University 3 , Augusta, GA 30912 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren M. F.","family":"Merlo","sequence":"additional","affiliation":[{"name":"Lankenau Institute for Medical Research 2 , Wynnewood, PA 19096 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Pigott","sequence":"additional","affiliation":[{"name":"Lankenau Institute for Medical Research 2 , Wynnewood, PA 19096 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin P.","family":"Keough","sequence":"additional","affiliation":[{"name":"Lankenau Institute for Medical Research 2 , Wynnewood, PA 19096 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Rust","sequence":"additional","affiliation":[{"name":"New Link Genetics Corporation 1 , Ames, IA 50010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew L.","family":"Mellor","sequence":"additional","affiliation":[{"name":"Immunotherapy Center, Georgia Regents University 3 , Augusta, GA 30912 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Mandik-Nayak","sequence":"additional","affiliation":[{"name":"Lankenau Institute for Medical Research 2 , Wynnewood, PA 19096 , USA"},{"name":"Department of Microbiology and Immunology 4 , Thomas Jefferson University, Philadelphia, PA 19107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander J.","family":"Muller","sequence":"additional","affiliation":[{"name":"Lankenau Institute for Medical Research 2 , Wynnewood, PA 19096 , USA"},{"name":"Kimmel Cancer Center 5 , Thomas Jefferson University, Philadelphia, PA 19107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George C.","family":"Prendergast","sequence":"additional","affiliation":[{"name":"Lankenau Institute for Medical Research 2 , Wynnewood, PA 19096 , USA"},{"name":"Kimmel Cancer Center 5 , Thomas Jefferson University, Philadelphia, PA 19107, USA"},{"name":"Department of Pathology, Anatomy and Cell Biology, Jefferson Medical School, Thomas Jefferson University 6 , Philadelphia, PA 19107 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,1,13]]},"reference":[{"key":"2022072023083825600_CIT0001","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.gene.2007.04.010","article-title":"Characterization of an indoleamine 2,3-dioxygenase-like protein found in humans and mice","volume":"396","author":"Ball","year":"2007","journal-title":"Gene"},{"key":"2022072023083825600_CIT0002","doi-asserted-by":"crossref","first-page":"7082","DOI":"10.1158\/0008-5472.CAN-07-1872","article-title":"Novel tryptophan catabolic enzyme IDO2 is the preferred biochemical target of the antitumor indoleamine 2,3-dioxygenase inhibitory compound D-1-methyl-tryptophan","volume":"67","author":"Metz","year":"2007","journal-title":"Cancer Res"},{"key":"2022072023083825600_CIT0003","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/nature10491","article-title":"An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor","volume":"478","author":"Opitz","year":"2011","journal-title":"Nature"},{"key":"2022072023083825600_CIT0004","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.2174\/092986711795656072","article-title":"Indoleamine 2,3-dioxygenase as a modifier of pathogenic inflammation in cancer and other inflammation-associated diseases","volume":"18","author":"Prendergast","year":"2011","journal-title":"Curr. Med. Chem"},{"key":"2022072023083825600_CIT0005","doi-asserted-by":"crossref","first-page":"2127","DOI":"10.1084\/jem.20120408","article-title":"Tryptophan hydroxylase-1 regulates immune tolerance and inflammation","volume":"209","author":"Nowak","year":"2012","journal-title":"J. Exp. Med"},{"key":"2022072023083825600_CIT0006","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1016\/j.jamcollsurg.2008.12.018","article-title":"Genotyping and expression analysis of IDO2 in human pancreatic cancer: a novel, active target","volume":"208","author":"Witkiewicz","year":"2009","journal-title":"J. Am. Coll. Surg"},{"key":"2022072023083825600_CIT0007","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.cbpb.2009.02.002","article-title":"Characterization and evolution of vertebrate indoleamine 2, 3-dioxygenases IDOs from monotremes and marsupials","volume":"153","author":"Yuasa","year":"2009","journal-title":"Comp. Biochem. Physiol. B. Biochem. Mol. 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