{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:02:38Z","timestamp":1789448558571,"version":"build-2803163510"},"reference-count":53,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:00:00Z","timestamp":1789171200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Key Research Project of the Shennong Laboratory","award":["SN01-2022-05"],"award-info":[{"award-number":["SN01-2022-05"]}]},{"name":"Basal research funds of Henan Academy of Agricultural Sciences","award":["2026ZC75"],"award-info":[{"award-number":["2026ZC75"]}]},{"name":"Basal research funds of Henan Academy of Agricultural Sciences","award":["2026BX54"],"award-info":[{"award-number":["2026BX54"]}]},{"DOI":"10.13039\/501100004761","name":"Henan Provincial Natural Science Foundation","doi-asserted-by":"crossref","award":["262300421464"],"award-info":[{"award-number":["262300421464"]}],"id":[{"id":"10.13039\/501100004761","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Indoleamine 2,3-dioxygenase 2 (IDO2) and tryptophan 2,3-dioxygenase (TDO2) are rate-limiting enzymes of the kynurenine pathway, well-characterized in mammals. Unlike all other vertebrates, chickens lack the IDO1 gene and exclusively rely on IDO2\/TDO2 for tryptophan (Trp) catabolism; however, their biochemical features and physiological regulatory functions remain poorly defined. Here, we integrated dietary Trp intervention, multi-omics profiling, recombinant enzyme kinetics, and in vitro\/inflammatory animal models to characterize chicken IDO2 and TDO2. Supplementary dietary Trp maintained circulating Trp homeostasis while activating hepatic kynurenine metabolism being associated with reduced PPAR signaling and altered lipid and energy balance. Hepatic combined IDO2\/TDO2 catalytic activity increased markedly with Trp supplementation; this increase was accompanied by only modest transcriptional upregulation of kynurenine pathway genes (including IDO2, TDO2, and KYNU) and no major changes in their protein abundance, indicating post-translational functional modulation. Recombinant enzyme assays demonstrated optimal activity at chicken physiological pH of 7.2 and temperature of 42 \u00b0C; chicken IDO2 displayed measurable catalytic efficiency, which was lower than that of chicken TDO2, whereas its human ortholog showed no detectable activity under the same conditions. Furthermore, LPS and APEC infection significantly suppressed the combined total IDO2\/TDO2 activity during inflammatory stress, revealing an avian-specific metabolic\u2013immune regulatory pattern. This work defines the unique biochemical and physiological functions of avian IDO2 and TDO2, offering mechanistic references for poultry nutritional regulation and disease control.<\/jats:p>","DOI":"10.3390\/ani16182874","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T09:34:01Z","timestamp":1789378441000},"page":"2874","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chicken IDO2 and TDO2: Biochemical Characteristics and Regulatory Roles in Avian Tryptophan Metabolism and Inflammatory Response"],"prefix":"10.3390","volume":"16","author":[{"given":"Wanli","family":"Li","sequence":"first","affiliation":[{"name":"Institute of Animal Husbandry, Henan Academy of Agricultural Sciences, Zhengzhou 450002, China"},{"name":"The Shennong Laboratory, Zhengzhou 450002, China"},{"name":"Henan Key Laboratory of Farm Animal Breeding and Nutritional Regulation, Zhengzhou 450002, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Chen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Animal Husbandry, Henan Academy of Agricultural Sciences, Zhengzhou 450002, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Pinhui","family":"Wu","sequence":"additional","affiliation":[{"name":"College of Life Science, Henan Agricultural University, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Kangfei","family":"Feng","sequence":"additional","affiliation":[{"name":"College of Life Science, Henan Agricultural University, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Guozhi","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Life Science, Henan Agricultural University, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8013-4313","authenticated-orcid":false,"given":"Lin","family":"Yuan","sequence":"additional","affiliation":[{"name":"Institute of Animal Husbandry, Henan Academy of Agricultural Sciences, Zhengzhou 450002, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Wei","family":"Jin","sequence":"additional","affiliation":[{"name":"Institute of Animal Husbandry, Henan Academy of Agricultural Sciences, Zhengzhou 450002, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Bingxun","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Animal Husbandry, Henan Academy of Agricultural Sciences, Zhengzhou 450002, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Shengli","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Animal Husbandry, Henan Academy of Agricultural Sciences, Zhengzhou 450002, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Life Science, Henan Agricultural University, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0186-9165","authenticated-orcid":false,"given":"Wenqing","family":"Li","sequence":"additional","affiliation":[{"name":"College of Life Science, Henan Agricultural University, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.tips.2017.11.007","article-title":"Targeting the IDO1\/TDO2-KYN-AhR Pathway for Cancer Immunotherapy-Challenges and Opportunities","volume":"39","author":"Cheong","year":"2018","journal-title":"Trends Pharmacol. 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