{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T03:01:12Z","timestamp":1777604472082,"version":"3.51.4"},"reference-count":51,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T00:00:00Z","timestamp":1663718400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T00:00:00Z","timestamp":1663718400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000062","name":"U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK108894"],"award-info":[{"award-number":["R01DK108894"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK124408"],"award-info":[{"award-number":["R01DK124408"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"name":"U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Unconjugated bilirubin (UCB) confers Th17-cells immunosuppressive features by activating aryl-hydrocarbon-receptor, a modulator of toxin and adaptive immune responses. In Crohn\u2019s disease, Th17-cells fail to acquire regulatory properties in response to UCB, remaining at an inflammatory\/pathogenic state. Here we show that UCB modulates Th17-cell metabolism by limiting glycolysis and through downregulation of glycolysis-related genes, namely phosphoglycerate-kinase-1 (<jats:italic>PGK1<\/jats:italic>) and aldolase-A (<jats:italic>ALDOA<\/jats:italic>). Th17-cells of Crohn\u2019s disease patients display heightened <jats:italic>PGK1<\/jats:italic> and <jats:italic>ALDOA<\/jats:italic> and defective response to UCB. Silencing of <jats:italic>PGK1<\/jats:italic> or <jats:italic>ALDOA<\/jats:italic> restores Th17-cell response to UCB, as reflected by increase in immunoregulatory markers like FOXP3, IL-10 and CD39. In vivo, <jats:italic>PGK1<\/jats:italic> and <jats:italic>ALDOA<\/jats:italic> silencing enhances UCB salutary effects in trinitro-benzene-sulfonic-acid-induced colitis in <jats:italic>NOD\/scid\/gamma<\/jats:italic> humanized mice where control over disease activity and enhanced immunoregulatory phenotypes are achieved. <jats:italic>PGK1<\/jats:italic> and\/or <jats:italic>ALDOA<\/jats:italic> blockade might have therapeutic effects in Crohn\u2019s disease by favoring acquisition of regulatory properties by Th17-cells along with control over their pathogenic potential.<\/jats:p>","DOI":"10.1038\/s42003-022-03913-9","type":"journal-article","created":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T12:04:13Z","timestamp":1663761853000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Blockade of PGK1 and ALDOA enhances bilirubin control of Th17 cells in Crohn\u2019s disease"],"prefix":"10.1038","volume":"5","author":[{"given":"Marta","family":"Vuerich","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9552-0524","authenticated-orcid":false,"given":"Na","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathon J.","family":"Graham","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmadreza","family":"Kalbasi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lina","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Csizmadia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason","family":"Hristopoulos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Efi","family":"Kokkotou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam S.","family":"Cheifetz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6374-0194","authenticated-orcid":false,"given":"Simon C.","family":"Robson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4510-1249","authenticated-orcid":false,"given":"Maria Serena","family":"Longhi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,9,21]]},"reference":[{"key":"3913_CR1","doi-asserted-by":"publisher","first-page":"1468","DOI":"10.1007\/BF02088574","volume":"41","author":"Y Haga","year":"1996","unstructured":"Haga, Y., Tempero, M. A., Kay, D. & Zetterman, R. K. Intracellular accumulation of unconjugated bilirubin inhibits phytohemagglutin-induced proliferation and interleukin-2 production of human lymphocytes. Dig. Dis. Sci. 41, 1468\u20131474 (1996).","journal-title":"Dig. Dis. Sci."},{"key":"3913_CR2","doi-asserted-by":"publisher","first-page":"1887","DOI":"10.4049\/jimmunol.181.3.1887","volume":"181","author":"Y Liu","year":"2008","unstructured":"Liu, Y. et al. Bilirubin possesses powerful immunomodulatory activity and suppresses experimental autoimmune encephalomyelitis. J. Immunol. 181, 1887\u20131897 (2008).","journal-title":"J. Immunol."},{"key":"3913_CR3","doi-asserted-by":"publisher","first-page":"443","DOI":"10.3727\/096368909X484680","volume":"19","author":"F Rocuts","year":"2010","unstructured":"Rocuts, F. et al. Bilirubin promotes de novo generation of T regulatory cells. Cell Transpl. 19, 443\u2013451 (2010).","journal-title":"Cell Transpl."},{"key":"3913_CR4","doi-asserted-by":"publisher","first-page":"3450","DOI":"10.1096\/fj.07-8472com","volume":"21","author":"SS Lee","year":"2007","unstructured":"Lee, S. S. et al. Heme oxygenase-1, carbon monoxide, and bilirubin induce tolerance in recipients toward islet allografts by modulating T regulatory cells. FASEB J. 21, 3450\u20133457 (2007).","journal-title":"FASEB J."},{"key":"3913_CR5","doi-asserted-by":"publisher","unstructured":"Longhi, M. S. et al. Bilirubin suppresses Th17 immunity in colitis by upregulating CD39. JCI Insight https:\/\/doi.org\/10.1172\/jci.insight.92791 (2017).","DOI":"10.1172\/jci.insight.92791"},{"key":"3913_CR6","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1038\/s41563-019-0462-9","volume":"19","author":"Y Lee","year":"2020","unstructured":"Lee, Y. et al. Hyaluronic acid-bilirubin nanomedicine for targeted modulation of dysregulated intestinal barrier, microbiome and immune responses in colitis. Nat. Mater. 19, 118\u2013126 (2020).","journal-title":"Nat. Mater."},{"key":"3913_CR7","doi-asserted-by":"publisher","first-page":"7460","DOI":"10.1002\/anie.201602525","volume":"55","author":"Y Lee","year":"2016","unstructured":"Lee, Y. et al. Bilirubin nanoparticles as a nanomedicine for anti-inflammation therapy. Angew. Chem. Int Ed. Engl. 55, 7460\u20137463 (2016).","journal-title":"Angew. Chem. Int Ed. Engl."},{"key":"3913_CR8","first-page":"5256460","volume":"2019","author":"X Zhao","year":"2019","unstructured":"Zhao, X. et al. The relationship between serum bilirubin and inflammatory bowel disease. Mediators Inflamm. 2019, 5256460 (2019).","journal-title":"Mediators Inflamm."},{"key":"3913_CR9","doi-asserted-by":"publisher","first-page":"6298","DOI":"10.12659\/MSM.909692","volume":"24","author":"S Tian","year":"2018","unstructured":"Tian, S., Li, J., Li, R., Liu, Z. & Dong, W. Decreased serum bilirubin levels and increased uric acid levels are associated with ulcerative colitis. Med. Sci. Monit. 24, 6298\u20136304 (2018).","journal-title":"Med. Sci. Monit."},{"key":"3913_CR10","doi-asserted-by":"publisher","first-page":"e15664","DOI":"10.1097\/MD.0000000000015664","volume":"98","author":"Q Su","year":"2019","unstructured":"Su, Q., Li, X., Mo, W. & Yang, Z. Low serum bilirubin, albumin, and uric acid levels in patients with Crohn\u2019s disease. Medicine 98, e15664 (2019).","journal-title":"Medicine"},{"key":"3913_CR11","doi-asserted-by":"publisher","first-page":"e0179267","DOI":"10.1371\/journal.pone.0179267","volume":"12","author":"KM Schieffer","year":"2017","unstructured":"Schieffer, K. M. et al. Reduced total serum bilirubin levels are associated with ulcerative colitis. PLoS ONE 12, e0179267 (2017).","journal-title":"PLoS ONE"},{"key":"3913_CR12","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1097\/01.MIB.0000440817.84251.98","volume":"20","author":"M Lenicek","year":"2014","unstructured":"Lenicek, M. et al. The relationship between serum bilirubin and Crohn\u2019s disease. Inflamm. Bowel Dis. 20, 481\u2013487 (2014).","journal-title":"Inflamm. Bowel Dis."},{"key":"3913_CR13","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1016\/j.crohns.2011.11.010","volume":"6","author":"HS de Vries","year":"2012","unstructured":"de Vries, H. S., Te Morsche, R. H., Jenniskens, K., Peters, W. H. & de Jong, D. J. A functional polymorphism in UGT1A1 related to hyperbilirubinemia is associated with a decreased risk for Crohn\u2019s disease. J. Crohns Colitis 6, 597\u2013602 (2012).","journal-title":"J. Crohns Colitis"},{"key":"3913_CR14","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1006\/abbi.1998.0814","volume":"357","author":"D Phelan","year":"1998","unstructured":"Phelan, D., Winter, G. M., Rogers, W. J., Lam, J. C. & Denison, M. S. Activation of the Ah receptor signal transduction pathway by bilirubin and biliverdin. Arch. Biochem. Biophys. 357, 155\u2013163 (1998).","journal-title":"Arch. Biochem. Biophys."},{"key":"3913_CR15","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1038\/nature06880","volume":"453","author":"FJ Quintana","year":"2008","unstructured":"Quintana, F. J. et al. Control of T(reg) and T(H)17 cell differentiation by the aryl hydrocarbon receptor. Nature 453, 65\u201371 (2008).","journal-title":"Nature"},{"key":"3913_CR16","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1038\/nature06881","volume":"453","author":"M Veldhoen","year":"2008","unstructured":"Veldhoen, M. et al. The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins. Nature 453, 106\u2013109 (2008).","journal-title":"Nature"},{"key":"3913_CR17","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.immuni.2017.12.012","volume":"48","author":"C Gutierrez-Vazquez","year":"2018","unstructured":"Gutierrez-Vazquez, C. & Quintana, F. J. Regulation of the immune response by the aryl hydrocarbon receptor. Immunity 48, 19\u201333 (2018).","journal-title":"Immunity"},{"key":"3913_CR18","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1016\/j.jaut.2018.07.022","volume":"94","author":"A Xie","year":"2018","unstructured":"Xie, A. et al. HIF-1alpha-induced xenobiotic transporters promote Th17 responses in Crohn\u2019s disease. J. Autoimmun. 94, 122\u2013133 (2018).","journal-title":"J. Autoimmun."},{"key":"3913_CR19","doi-asserted-by":"publisher","first-page":"1739","DOI":"10.1289\/ehp.1103593","volume":"119","author":"C Wang","year":"2011","unstructured":"Wang, C. et al. Aryl hydrocarbon receptor deficiency enhances insulin sensitivity and reduces PPAR-alpha pathway activity in mice. Environ. Health Perspect. 119, 1739\u20131744 (2011).","journal-title":"Environ. Health Perspect."},{"key":"3913_CR20","doi-asserted-by":"publisher","first-page":"12398","DOI":"10.1074\/jbc.AC120.014189","volume":"295","author":"MC Lafita-Navarro","year":"2020","unstructured":"Lafita-Navarro, M. C. et al. The transcription factors aryl hydrocarbon receptor and MYC cooperate in the regulation of cellular metabolism. J. Biol. Chem. 295, 12398\u201312407 (2020).","journal-title":"J. Biol. Chem."},{"key":"3913_CR21","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-0297-3","volume":"9","author":"Q Lv","year":"2018","unstructured":"Lv, Q. et al. Norisoboldine, a natural AhR agonist, promotes Treg differentiation and attenuates colitis via targeting glycolysis and subsequent NAD(+)\/SIRT1\/SUV39H1\/H3K9me3 signaling pathway. Cell Death Dis. 9, 258 (2018).","journal-title":"Cell Death Dis."},{"key":"3913_CR22","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19692-y","volume":"11","author":"RP Harshe","year":"2020","unstructured":"Harshe, R. P. et al. Endogenous antisense RNA curbs CD39 expression in Crohn\u2019s disease. Nat. Commun. 11, 5894 (2020).","journal-title":"Nat. Commun."},{"key":"3913_CR23","doi-asserted-by":"publisher","first-page":"1070","DOI":"10.4049\/jimmunol.1501310","volume":"196","author":"L Meng","year":"2016","unstructured":"Meng, L. et al. The Notch ligand DLL4 defines a capability of human dendritic cells in regulating Th1 and Th17 differentiation. J. Immunol. 196, 1070\u20131080 (2016).","journal-title":"J. Immunol."},{"key":"3913_CR24","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1210\/en.2009-0726","volume":"151","author":"C Ribet","year":"2010","unstructured":"Ribet, C. et al. Peroxisome proliferator-activated receptor-alpha control of lipid and glucose metabolism in human white adipocytes. Endocrinology 151, 123\u2013133 (2010).","journal-title":"Endocrinology"},{"key":"3913_CR25","doi-asserted-by":"publisher","first-page":"781","DOI":"10.3109\/1061186X.2011.568062","volume":"19","author":"G Venkatachalam","year":"2011","unstructured":"Venkatachalam, G. et al. PPARgamma disease gene network and identification of therapeutic targets for prostate cancer. J. Drug Target 19, 781\u2013796 (2011).","journal-title":"J. Drug Target"},{"key":"3913_CR26","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1038\/nature11862","volume":"493","author":"LA O\u2019Neill","year":"2013","unstructured":"O\u2019Neill, L. A. & Hardie, D. G. Metabolism of inflammation limited by AMPK and pseudo-starvation. Nature 493, 346\u2013355 (2013).","journal-title":"Nature"},{"key":"3913_CR27","doi-asserted-by":"publisher","unstructured":"Sun, X. & Zhu, M. J. AMP-activated protein kinase: a therapeutic target in intestinal diseases. Open Biol. https:\/\/doi.org\/10.1098\/rsob.170104 (2017).","DOI":"10.1098\/rsob.170104"},{"key":"3913_CR28","doi-asserted-by":"publisher","first-page":"1605","DOI":"10.2174\/0929867327666200504081503","volume":"28","author":"NA Lashgari","year":"2021","unstructured":"Lashgari, N. A. et al. Targeting mammalian target of rapamycin: prospects for the treatment of inflammatory bowel diseases. Curr. Med. Chem. 28, 1605\u20131624 (2021).","journal-title":"Curr. Med. Chem."},{"key":"3913_CR29","doi-asserted-by":"publisher","first-page":"122","DOI":"10.3389\/fcell.2018.00122","volume":"6","author":"RJ Salmond","year":"2018","unstructured":"Salmond, R. J. mTOR regulation of glycolytic metabolism in T cells. Front. Cell Dev. Biol. 6, 122 (2018).","journal-title":"Front. Cell Dev. Biol."},{"key":"3913_CR30","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1111\/1751-2980.12095","volume":"14","author":"SH Long","year":"2013","unstructured":"Long, S. H. et al. Activation of PI3K\/Akt\/mTOR signaling pathway triggered by PTEN downregulation in the pathogenesis of Crohn\u2019s disease. J. Dig. Dis. 14, 662\u2013669 (2013).","journal-title":"J. Dig. Dis."},{"key":"3913_CR31","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1093\/ecco-jcc\/jjz182","volume":"14","author":"RJ Robles","year":"2020","unstructured":"Robles, R. J. et al. Modulation of CD39 and exogenous APT102 correct immune dysfunction in experimental colitis and Crohn\u2019s disease. J. Crohns Colitis 14, 818\u2013830 (2020).","journal-title":"J. Crohns Colitis"},{"key":"3913_CR32","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1016\/j.cell.2020.06.014","volume":"182","author":"L Wu","year":"2020","unstructured":"Wu, L. et al. Niche-selective inhibition of pathogenic Th17 cells by targeting metabolic redundancy. Cell 182, 641\u2013654 e620 (2020).","journal-title":"Cell"},{"key":"3913_CR33","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.immuni.2019.05.004","volume":"51","author":"S Omenetti","year":"2019","unstructured":"Omenetti, S. et al. The intestine harbors functionally distinct homeostatic tissue-resident and inflammatory Th17 cells. Immunity 51, 77\u201389 e76 (2019).","journal-title":"Immunity"},{"key":"3913_CR34","doi-asserted-by":"publisher","first-page":"618365","DOI":"10.3389\/fimmu.2021.618365","volume":"12","author":"PJ Basso","year":"2021","unstructured":"Basso, P. J. et al. Peroxisome proliferator-activated receptor alpha mediates the beneficial effects of atorvastatin in experimental colitis. Front. Immunol. 12, 618365 (2021).","journal-title":"Front. Immunol."},{"key":"3913_CR35","doi-asserted-by":"publisher","first-page":"128361","DOI":"10.1016\/j.bmcl.2021.128361","volume":"51","author":"Y Zhao","year":"2021","unstructured":"Zhao, Y. et al. Discovery of bilirubin as novel P2X7R antagonist with anti-tumor activity. Bioorg. Med. Chem. Lett. 51, 128361 (2021).","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"3913_CR36","doi-asserted-by":"publisher","first-page":"e87956","DOI":"10.1371\/journal.pone.0087956","volume":"9","author":"MS Longhi","year":"2014","unstructured":"Longhi, M. S. et al. Characterization of human CD39+ Th17 cells with suppressor activity and modulation in inflammatory bowel disease. PLoS ONE 9, e87956 (2014).","journal-title":"PLoS ONE"},{"key":"3913_CR37","doi-asserted-by":"publisher","first-page":"16788","DOI":"10.1073\/pnas.0902869106","volume":"106","author":"DJ Friedman","year":"2009","unstructured":"Friedman, D. J. et al. From the cover: CD39 deletion exacerbates experimental murine colitis and human polymorphisms increase susceptibility to inflammatory bowel disease. Proc. Natl Acad. Sci. USA 106, 16788\u201316793 (2009).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"3913_CR38","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1002\/hep.25989","volume":"57","author":"X Sun","year":"2013","unstructured":"Sun, X. et al. Disordered purinergic signaling and abnormal cellular metabolism are associated with development of liver cancer in Cd39\/ENTPD1 null mice. Hepatology 57, 205\u2013216 (2013).","journal-title":"Hepatology"},{"key":"3913_CR39","doi-asserted-by":"publisher","first-page":"726128","DOI":"10.3389\/fphar.2021.726128","volume":"12","author":"C Huang","year":"2021","unstructured":"Huang, C. et al. Glucose metabolism reprogramming of regulatory T cells in concanavalin A-induced hepatitis. Front. Pharm. 12, 726128 (2021).","journal-title":"Front. Pharm."},{"key":"3913_CR40","doi-asserted-by":"publisher","first-page":"1186","DOI":"10.1038\/s42003-021-02721-x","volume":"4","author":"LB Jarvis","year":"2021","unstructured":"Jarvis, L. B. et al. Therapeutically expanded human regulatory T-cells are super-suppressive due to HIF1A induced expression of CD73. Commun. Biol. 4, 1186 (2021).","journal-title":"Commun. Biol."},{"key":"3913_CR41","doi-asserted-by":"publisher","unstructured":"Damasceno, L. E. A. et al. PKM2 promotes Th17 cell differentiation and autoimmune inflammation by fine-tuning STAT3 activation. J. Exp. Med. https:\/\/doi.org\/10.1084\/jem.20190613 (2020).","DOI":"10.1084\/jem.20190613"},{"key":"3913_CR42","doi-asserted-by":"publisher","unstructured":"Kono, M. et al. Pyruvate kinase M2 is requisite for Th1 and Th17 differentiation. JCI Insight https:\/\/doi.org\/10.1172\/jci.insight.127395 (2019).","DOI":"10.1172\/jci.insight.127395"},{"key":"3913_CR43","doi-asserted-by":"publisher","first-page":"1693","DOI":"10.1136\/gutjnl-2011-301668","volume":"61","author":"W Hueber","year":"2012","unstructured":"Hueber, W. et al. Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn\u2019s disease: unexpected results of a randomised, double-blind placebo-controlled trial. Gut 61, 1693\u20131700 (2012).","journal-title":"Gut"},{"key":"3913_CR44","doi-asserted-by":"publisher","first-page":"1610","DOI":"10.1111\/apt.14669","volume":"47","author":"JR White","year":"2018","unstructured":"White, J. R. et al. Review article: novel oral-targeted therapies in inflammatory bowel disease. Aliment Pharm. Ther. 47, 1610\u20131622 (2018).","journal-title":"Aliment Pharm. Ther."},{"key":"3913_CR45","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1016\/j.tips.2014.07.006","volume":"35","author":"J Yang","year":"2014","unstructured":"Yang, J., Sundrud, M. S., Skepner, J. & Yamagata, T. Targeting Th17 cells in autoimmune diseases. Trends Pharm. Sci. 35, 493\u2013500 (2014).","journal-title":"Trends Pharm. Sci."},{"key":"3913_CR46","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1136\/gut.2005.082909","volume":"55","author":"J Satsangi","year":"2006","unstructured":"Satsangi, J., Silverberg, M. S., Vermeire, S. & Colombel, J. F. The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications. Gut 55, 749\u2013753 (2006).","journal-title":"Gut"},{"key":"3913_CR47","doi-asserted-by":"publisher","first-page":"263","DOI":"10.3109\/10799893.2012.703674","volume":"32","author":"B Oleszczak","year":"2012","unstructured":"Oleszczak, B., Szablewski, L. & Pliszka, M. The effect of glucose concentrations in the medium on expression of insulin receptors in human lymphocytes B and T: an in vitro study. J. Recept. Signal Transduct. Res. 32, 263\u2013270 (2012).","journal-title":"J. Recept. Signal Transduct. Res."},{"key":"3913_CR48","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1038\/labinvest.2011.160","volume":"92","author":"F Moriconi","year":"2012","unstructured":"Moriconi, F. et al. The anti-TNF-alpha antibody infliximab indirectly regulates PECAM-1 gene expression in two models of in vitro blood cell activation. Lab Invest. 92, 166\u2013177 (2012).","journal-title":"Lab Invest."},{"key":"3913_CR49","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1177\/0885066618789114","volume":"35","author":"MJ Holmberg","year":"2020","unstructured":"Holmberg, M. J. et al. Ubiquinol (reduced coenzyme Q10) and cellular oxygen consumption in patients undergoing coronary artery bypass grafting. J. Intensive Care Med. 35, 797\u2013804 (2020).","journal-title":"J. Intensive Care Med."},{"key":"3913_CR50","doi-asserted-by":"publisher","unstructured":"Liu, X. et al. The effects of thiamine on breast cancer cells. Molecules https:\/\/doi.org\/10.3390\/molecules23061464 (2018).","DOI":"10.3390\/molecules23061464"},{"key":"3913_CR51","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.jaut.2016.05.005","volume":"72","author":"R Liberal","year":"2016","unstructured":"Liberal, R. et al. CD39 mediated regulation of Th17-cell effector function is impaired in juvenile autoimmune liver disease. J. Autoimmun. 72, 102\u2013112 (2016).","journal-title":"J. Autoimmun."}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-022-03913-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-022-03913-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-022-03913-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T12:15:56Z","timestamp":1663762556000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-022-03913-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,21]]},"references-count":51,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["3913"],"URL":"https:\/\/doi.org\/10.1038\/s42003-022-03913-9","relation":{},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,21]]},"assertion":[{"value":"3 March 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 August 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 September 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"994"}}