{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T18:43:04Z","timestamp":1791916984997,"version":"4.3.4"},"reference-count":43,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,6,8]],"date-time":"2022-06-08T00:00:00Z","timestamp":1654646400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81900124"],"award-info":[{"award-number":["81900124"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82030005"],"award-info":[{"award-number":["82030005"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2019BH055"],"award-info":[{"award-number":["ZR2019BH055"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2021MH115"],"award-info":[{"award-number":["ZR2021MH115"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Immune thrombocytopenia (ITP) is an acquired autoimmune disease, in which the imbalance of CD4<jats:sup>+<\/jats:sup> T cell subsets play a key role in the pathogenesis. Since T cells highly depend on metabolism for their function, we hypothesized that T cell dysfunction may be due to intracellular metabolic reprogramming. We found that in ITP, T cell metabolism shifts from oxidative phosphorylation to glycolysis. Empagliflozin, a sodium\u2013glucose cotransporter 2 inhibitor, has shown regulatory metabolic effects on proximal tubular epithelial cells and cardiac cells beyond glucose lowering. However, the effects of empagliflozin on T cells remain unknown. To further investigate the metabolic dysfunction of CD4<jats:sup>+<\/jats:sup> T cells in ITP, we explored the effect of empagliflozin on CD4<jats:sup>+<\/jats:sup> T\u2010cell differentiation in ITP. Our results are the first to show that increased glycolysis in CD4<jats:sup>+<\/jats:sup> T cells resulted in an unbalanced CD4<jats:sup>+<\/jats:sup> T\u2010cell population. Furthermore, empagliflozin can affect the differentiation of CD4<jats:sup>+<\/jats:sup> T\u2010cell subsets by inhibiting Th1 and Th17 cell populations while increasing Tregs. Empagliflozin appears to regulate CD4<jats:sup>+<\/jats:sup> T cells through inhibiting the mTOR signal pathway. Considering these results, we propose that empagliflozin could be used as a potential therapeutic option for ITP by modulating metabolic reprogramming in CD4<jats:sup>+<\/jats:sup> T cells.<\/jats:p>","DOI":"10.1111\/bjh.18293","type":"journal-article","created":{"date-parts":[[2022,6,8]],"date-time":"2022-06-08T18:19:20Z","timestamp":1654712360000},"page":"765-775","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Empagliflozin modulates CD4<sup>+<\/sup> T\u2010cell differentiation via metabolic reprogramming in immune thrombocytopenia"],"prefix":"10.1111","volume":"198","author":[{"given":"Jing","family":"Qin","sequence":"first","affiliation":[{"name":"Department of Hematology, Qilu Hospital Cheeloo College of Medicine, Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Hematology, Qilu Hospital Cheeloo College of Medicine, Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anli","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Hematology, Qilu Hospital Cheeloo College of Medicine, Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoqiu","family":"Leng","sequence":"additional","affiliation":[{"name":"Department of Hematology, Qilu Hospital Cheeloo College of Medicine, Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuwen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hematology, Qilu Hospital Cheeloo College of Medicine, Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0612-164X","authenticated-orcid":false,"given":"Chaoyang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hematology, Qilu Hospital Cheeloo College of Medicine, Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Shandong Cancer Hospital and Institute First Medical University and Shandong Academy of Medical Science  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Hematology, Qilu Hospital Cheeloo College of Medicine, Shandong University  Jinan China"},{"name":"State Key Laboratory of Experimental Hematology Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2981-9533","authenticated-orcid":false,"given":"Miao","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Hematology, Qilu Hospital Cheeloo College of Medicine, Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,6,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102009\u201001\u2010129155"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12325\u2010015\u20100251\u2010z"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2012.04.015"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875\u2010012\u20109649\u20104"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00277\u2010008\u20100535\u20103"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102003\u201007\u20102268"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3268"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102008\u201001\u2010135335"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.7.4476"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.09.021"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010immunol\u2010032712\u2010095956"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1710"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1074\u20107613(02)00323\u20100"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.07.008"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1003613"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0000000000000687"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2018.04.006"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2017.43"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2019.07.001"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2014.12.004"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2017.04.006"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3180"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2017.01.035"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.104870"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.10.020"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2012.12.004"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.01020"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.09.015"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2005"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.04.014"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1939"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102004\u201010\u20103932"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1207851"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2020.06.020"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOH.0b013e3283567541"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2016.10.009"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1501766"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3704"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201546152"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.111902"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.31193"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabet.2020.06.005"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.645483"}],"container-title":["British Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bjh.18293","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bjh.18293","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bjh.18293","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T22:01:14Z","timestamp":1692741674000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bjh.18293"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,8]]},"references-count":43,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2022,8]]}},"alternative-id":["10.1111\/bjh.18293"],"URL":"https:\/\/doi.org\/10.1111\/bjh.18293","archive":["Portico"],"relation":{},"ISSN":["0007-1048","1365-2141"],"issn-type":[{"value":"0007-1048","type":"print"},{"value":"1365-2141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,8]]},"assertion":[{"value":"2022-02-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}