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. 2020 Jun 6;17:176. doi: 10.1186/s12974-020-01844-y

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© The Author(s) 2020

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 6 — Delayed modulation of KP reverses the progression of experimental autoimmune encephalomyelitis (EAE). a Schematic illustration of kynurenine pathway (KP). b Mean EAE clinical scores of healthy control (◊, n = 6), untreated EAE control (Δ, n = 6), and Ro 61-8048 treated EAE mice (KMO inhibitor; O; n = 6), 100 mg/kg; i.p. daily for 7 days (mean ± SD, *p < 0.05 (Ro 618048 vs untreated EAE)). c and d The heat maps show KP gene expression in the brain (c) and spinal cord (d) of healthy, untreated and Ro 61 8048 treated EAE mice. Gene expression ranges from high (dark blue) to low (white). e FoxP3 (forkhead box protein) expression was measured in spleen of 1-MT and Ro 61-8048 treated EAE-induced mice (EAE score 2). f–h Changes in KP metabolites upon treatment with Ro 61-8048. The line diagrams depict kynurenine and tryptophan (KYN/TRP) ratio (f), kynurenic acid, and quinolinic acid (KYNA/QUIN) ratio (g), and picolinic acid and quinolinic acid (PIC/QUIN) ratio (h) measured (mean ± SD) in the plasma, brain, and spinal cord of healthy (white; n = 8), untreated EAE (black; n = 6), and Ro 61-8048 (gray; n = 3) treated mice. Three symbols: p ≤ 0.001; two: p ≤ 0.01; one: p ≤ 0.05. IDO-1, indoleamine 2,3-dioxygenase; KAT, kynurenine amino transferase; KYNU, kynureninase; KMO, kynurenine monooxygenase; 3HAO, 3-hydroxyanthranilate 3,4-dioxygenase; ACMSD, 2-amino-3-carboxymuconatesemialdehyde decarboxylase; QPRT, quinolinate phosphoribosyl transferase