{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:27:09Z","timestamp":1787030829850,"version":"build-2736575974"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T00:00:00Z","timestamp":1736121600000},"content-version":"vor","delay-in-days":1680,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>CTLA4Ig, a reagent that inhibits CD28 signaling, has shown therapeutic efficacy in mouse models of lupus nephritis (LN) when combined with several other biologics or standard of care drugs. Unfortunately, clinical trials treating LN patients with CTLA4Ig (abatacept) have not met endpoints. Metformin, a drug used to control hyperglycemia that inhibits mitochondrial metabolism, lowered the effective dose of glucocorticoids and prevented major flares when added on to the standard of care treatment of lupus patients with low disease activity. Metformin combined with inhibition of glycolysis by 2-deoxyglucose showed therapeutic efficacy in multiple mouse models of LN. Because CD28 signaling triggers glucose metabolism in T cells, we hypothesized that combining CTLA4Ig treatment with metformin would have the same effect. In this study, we showed that the combination of metformin and CTLA4Ig decreased the development of LN in (NZB \u00d7 NZW)F1 mice treated at the early stage of disease. This preventive effect was associated with a decreased expansion of CD4+ T cell effector subsets. However, contrary to the combination with 2-deoxyglucose, metformin combined with CTLA4Ig did not alter autoantibody production, suggesting different mechanisms of symptom mitigation. Overall, this study shows therapeutic efficacy of the combination of metformin and CTLA4Ig, two drugs with established safety records, in a preclinical mouse model of LN.<\/jats:p>","DOI":"10.4049\/immunohorizons.2000033","type":"journal-article","created":{"date-parts":[[2020,6,15]],"date-time":"2020-06-15T17:02:37Z","timestamp":1592240557000},"page":"319-331","source":"Crossref","is-referenced-by-count":22,"title":["Efficacy of the Combination of Metformin and CTLA4Ig in the (NZB \u00d7 NZW)F1 Mouse Model of Lupus Nephritis"],"prefix":"10.1093","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1098-1378","authenticated-orcid":false,"given":"Caleb","family":"Cornaby","sequence":"first","affiliation":[{"name":"Department of Pathology, Immunology and Laboratory Medicine, University of Florida , Gainesville, FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3759-6832","authenticated-orcid":false,"given":"Ahmed S","family":"Elshikha","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology and Laboratory Medicine, University of Florida , Gainesville, FL 32610"},{"name":"Department of Pharmaceutics, Zagazig University , Zagazig, Sharkia 44519 ,","place":["Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyu","family":"Teng","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology and Laboratory Medicine, University of Florida , Gainesville, FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6230-9087","authenticated-orcid":false,"given":"Seung-Chul","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology and Laboratory Medicine, University of Florida , Gainesville, FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6382-6289","authenticated-orcid":false,"given":"Yogesh","family":"Scindia","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Florida , Gainesville, FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Davidson","sequence":"additional","affiliation":[{"name":"Feinstein Institutes for Medical Research , Manhasset, NY 11030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Morel","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology and Laboratory Medicine, University of Florida , Gainesville, FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,6,16]]},"reference":[{"key":"2025010608422196000_r1","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1038\/s41584-019-0235-5","article-title":"New therapies for systemic lupus erythematosus - past imperfect, future tense. 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