{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T03:22:32Z","timestamp":1791256952881,"version":"4.1.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2010,11,1]],"date-time":"2010-11-01T00:00:00Z","timestamp":1288569600000},"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":[[2010,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Experimental autoimmune encephalomyelitis (EAE) is a Th1 and Th17 cell-mediated autoimmune disease of the CNS. IDO and tryptophan metabolites have inhibitory effects on Th1 cells in EAE. For Th17 cells, IDO-mediated tryptophan deprivation and small molecule halofuginone-induced amino acid starvation response were shown to activate general control nonrepressed 2 (GCN2) kinase that directly or indirectly inhibits Th17 cell differentiation. However, it remains unclear whether IDO and tryptophan metabolites impact the Th17 cell response by mechanisms other than the GCN2 kinase pathway. In this article, we show that IDO-deficient mice develop exacerbated EAE with enhanced encephalitogenic Th1 and Th17 cell responses and reduced regulatory T cell (Treg) responses. Administration of the downstream tryptophan metabolite 3-hydroxyanthranillic acid (3-HAA) enhanced the percentage of Tregs, inhibited Th1 and Th17 cells, and ameliorated EAE. We further demonstrate that Th17 cells are less sensitive to direct suppression by 3-HAA than are Th1 cells. 3-HAA treatment in vitro reduced IL-6 production by activated spleen cells and increased expression of TGF-\u03b2 in dendritic cells (DCs), which correlated with enhanced levels of Tregs, suggesting that 3-HAA\u2013induced Tregs contribute to inhibition of Th17 cells. By using a DC\u2013T cell coculture, we found that 3-HAA\u2013treated DCs expressed higher levels of TGF-\u03b2 and had properties to induce generation of Tregs from anti-CD3\/anti-CD28\u2013stimulated naive CD4+ T cells. Thus, our data support the hypothesis that IDO induces the generation of Tregs via tryptophan metabolites, such as 3-HAA, which enhances TGF-\u03b2 expression from DCs and promotes Treg differentiation.<\/jats:p>","DOI":"10.4049\/jimmunol.1001628","type":"journal-article","created":{"date-parts":[[2010,10,14]],"date-time":"2010-10-14T03:22:44Z","timestamp":1287026564000},"page":"5953-5961","source":"Crossref","is-referenced-by-count":336,"title":["IDO Upregulates Regulatory T Cells via Tryptophan Catabolite and Suppresses Encephalitogenic T Cell Responses in Experimental Autoimmune Encephalomyelitis"],"prefix":"10.1093","volume":"185","author":[{"given":"Yaping","family":"Yan","sequence":"first","affiliation":[{"name":"Department of Neurology, Thomas Jefferson University , Philadelphia, PA 19107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang-Xian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Thomas Jefferson University , Philadelphia, PA 19107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Gran","sequence":"additional","affiliation":[{"name":"Division of Clinical Neurology, University of Nottingham , Nottingham ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Fallarino","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine and Biochemical Sciences, University of Perugia , Perugia ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Thomas Jefferson University , Philadelphia, PA 19107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongmei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, Thomas Jefferson University , Philadelphia, PA 19107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa L","family":"Cullimore","sequence":"additional","affiliation":[{"name":"Department of Neurology, Thomas Jefferson University , Philadelphia, PA 19107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdolmohamad","family":"Rostami","sequence":"additional","affiliation":[{"name":"Department of Neurology, Thomas Jefferson University , Philadelphia, PA 19107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Thomas Jefferson University , Philadelphia, PA 19107"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,11,15]]},"reference":[{"key":"2025032412081373900_r1","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1038\/nri2190","article-title":"The origin and application of experimental autoimmune encephalomyelitis","volume":"7","author":"Baxter","year":"2007","journal-title":"Nat. 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