{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T03:02:39Z","timestamp":1789354959975,"version":"build-2803163510"},"reference-count":37,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T00:00:00Z","timestamp":1789257600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T00:00:00Z","timestamp":1789257600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82002214"],"award-info":[{"award-number":["82002214"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Systemic lupus erythematosus (SLE) is a complex autoimmune disorder driven by aberrant immune responses, predominately CD4\u2009+\u2009T cells dysfunction. CD73, an ecto\u20105\u2032\u2010nucleotidase mediating adenosine signalling, is essential for immune regulation. Herein, we investigated CD73 expression across CD4\u2009+\u2009T subpopulations and further explored their potential impacts on the activation and function of CD4\u2009+\u2009T subsets, together with their associations with disease activity and clinical features of SLE. A total of 134 SLE patients, 84 disease controls antiphospholipid syndrome (APS), and 61 healthy controls (HCs) were recruited. Flow cytometry was used to profile CD73 expression across circulating CD4\u2009+\u2009T subsets. Disease activity was assessed by SLEDAI\u20102\u2009K score. We identified a subset\u2010specific distribution pattern of CD73 expression in SLE compared with HCs, characterized by increased CD73 expression in Th1 and Th17 cells and reduced expression in Th2, Tregs, Tfh and Tfr cells. Meanwhile, significant elevated CD73\u2010expressing Th1\/Th2 ratios and obviously reduced CD73\u2010expressing Tfh\/Tfr ratios in SLE were observed. CD73\u2010expressing Th1 cells exhibited enhanced activation phenotype manifested as elevated expression of CD25, ICOS, PD\u20101, and secretion of IFN\u2010\n                    <jats:italic>\u03b3<\/jats:italic>\n                    . Positive correlation was observed between CD73\u2010expressing Th1 cells and CD25 expression within Th1 cells. In addition, CD73\u2010expressing Tph cells displayed reduced secretion of IFN\u2010\n                    <jats:italic>\u03b3<\/jats:italic>\n                    and IL\u201021, and positive association was found between CD73 expression and IL\u201021 secretion within Tph cells. Importantly, frequencies of CD73\u2010expressing Th1, Th2 and Tph cells were significantly reduced in active disease group relative to inactive group, and negatively correlated with SLEDAI\u20102\u2009K scores, and CD73\u2010expressing Th1 cells displayed moderate discriminatory capacity (AUC\u2009=\u20090.671) to differentiate active and inactive SLE. Furthermore, SLE patients with lupus nephritis showed decreased CD73\u2010expressing Th1 cells and Tph cells, and Tph cells was diminished in patients with thrombocytopenia. These findings highlighted CD73 as a potential marker of immune dysregulation, which may be associated with the activation\u2010 and function\u2010related cellular phenotypes. Aberrant CD73 expression may potentially be associated with disease activity and clinical manifestations of SLE patients.\n                  <\/jats:p>","DOI":"10.1111\/imm.70201","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T02:05:02Z","timestamp":1789351502000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Redistribution of\n                    <scp>CD73<\/scp>\n                    Expression on CD4+T Subpopulations in Systemic Lupus Erythematosus and Its Association With Disease Activity"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-0670-4186","authenticated-orcid":false,"given":"Rui","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory Peking University People's Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2811-8930","authenticated-orcid":false,"given":"Wen\u2010jie","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Peking University People's Hospital  Beijing China"},{"name":"Department of Clinical Laboratory Tangshan Workers' Hospital  Tangshan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun\u2010xian","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Peking University People's Hospital  Beijing China"},{"name":"Department of Clinical Laboratory Dali Bai Autonomous Prefecture Chinese Medicine Hospital  Dali China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6347-7328","authenticated-orcid":false,"given":"Zhan\u2010hong","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology Peking University People's Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing\u2010hong","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Peking University People's Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010yi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Peking University People's Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Long","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Peking University People's Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,13]]},"reference":[{"key":"e_1_2_9_2_1","volume-title":"Systemic Lupus Erythematosus. Statpearls","author":"Justiz Vaillant A. A.","year":"2025"},{"issue":"1","key":"e_1_2_9_3_1","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1136\/annrheumdis-2020-218272","article-title":"Update On the Diagnosis and Management of Systemic Lupus Erythematosus","volume":"80","author":"Fanouriakis A.","year":"2021","journal-title":"Annals of the Rheumatic Diseases"},{"issue":"6","key":"e_1_2_9_4_1","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1097\/BOR.0000000000000815","article-title":"The Role of Cd8+ T\u2010Cell Systemic Lupus Erythematosus Pathogenesis: An Update","volume":"33","author":"Chen P. M.","year":"2021","journal-title":"Current Opinion in Rheumatology"},{"issue":"20","key":"e_1_2_9_5_1","doi-asserted-by":"crossref","DOI":"10.3390\/ijms232012209","article-title":"Altered Circulating Follicular T Helper Cell Subsets and Follicular T Regulatory Cells Are Indicators of a Derailed B Cell Response in Lupus, Which Could be Modified by Targeting Il\u201021r","volume":"23","author":"Szab\u00f3 K.","year":"2022","journal-title":"International Journal of Molecular Sciences"},{"issue":"1","key":"e_1_2_9_6_1","first-page":"65","article-title":"Th17\/Treg Ratio and Disease Activity in Systemic Lupus Erythematosus","volume":"10","author":"Yuliasih Y.","year":"2019","journal-title":"Caspian Journal of Internal Medicine"},{"key":"e_1_2_9_7_1","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.clim.2018.08.005","article-title":"Th1\/17 Cells, a Subset of Th17 Cells, Are Expanded in Patients With Active Systemic Lupus Erythematosus","volume":"195","author":"Tsanaktsi A.","year":"2018","journal-title":"Clinical Immunology"},{"key":"e_1_2_9_8_1","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.clim.2016.04.010","article-title":"T Cells and Il\u201017 in Lupus Nephritis","volume":"185","author":"Koga T.","year":"2017","journal-title":"Clinical Immunology"},{"issue":"3","key":"e_1_2_9_9_1","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1111\/cei.12991","article-title":"Two Separate Effects Contribute to Regulatory T Cell Defect in Systemic Lupus Erythematosus Patients and Their Unaffected Relatives","volume":"189","author":"Costa N.","year":"2017","journal-title":"Clinical and Experimental Immunology"},{"issue":"10","key":"e_1_2_9_10_1","doi-asserted-by":"crossref","first-page":"4462","DOI":"10.1073\/pnas.1809329116","article-title":"Pivotal Role for \u0391(V) Integrins in Sustained Tfh Support of the Germinal Center Response for Long\u2010Lived Plasma Cell Generation","volume":"116","author":"Schrock D. C.","year":"2019","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"e_1_2_9_11_1","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.clim.2017.07.004","article-title":"The Ratio of Circulating Follicular T Helper Cell to Follicular T Regulatory Cell Is Correlated With Disease Activity in Systemic Lupus Erythematosus","volume":"183","author":"Xu B.","year":"2017","journal-title":"Clinical Immunology"},{"issue":"20","key":"e_1_2_9_12_1","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.130062","article-title":"PD\u20101hiCXCR5\u2010 T Peripheral Helper Cells Promote B Cell Responses in Lupus via Maf and Il\u201021","volume":"4","author":"Bocharnikov A. V.","year":"2019","journal-title":"JCI Insight"},{"issue":"10","key":"e_1_2_9_13_1","first-page":"1861","article-title":"Expanded Circulating Peripheral Helper T Cells in Systemic Lupus Erythematosus: Association With Disease Activity and B Cell Differentiation","volume":"58","author":"Makiyama A.","year":"2019","journal-title":"Rheumatology (Oxford)"},{"key":"e_1_2_9_14_1","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2022.914799","article-title":"The Multifaceted Actions of Cd73 During Development and Suppressive Actions of Regulatory T Cells","volume":"13","author":"Da M.","year":"2022","journal-title":"Frontiers in Immunology"},{"key":"e_1_2_9_15_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.ebiom.2021.103616","article-title":"Profound Inhibition of Cd73\u2010Dependent Formation of Anti\u2010Inflammatory Adenosine in B Cells of Sle Patients","volume":"73","author":"Hesse J.","year":"2021","journal-title":"eBioMedicine"},{"issue":"1","key":"e_1_2_9_16_1","doi-asserted-by":"crossref","first-page":"458","DOI":"10.4049\/jimmunol.1201325","article-title":"Adenosine a2a Receptor Agonist\u2010Mediated Increase in Donor\u2010Derived Regulatory T Cells Suppresses Development of Graft\u2010Versus\u2010Host Disease","volume":"190","author":"Han K. L.","year":"2013","journal-title":"Journal of Immunology"},{"issue":"25","key":"e_1_2_9_17_1","doi-asserted-by":"crossref","first-page":"2955","DOI":"10.3748\/wjg.v28.i25.2955","article-title":"Upregulated Adenosine 2a Receptor Accelerates Post\u2010Infectious Irritable Bowel Syndrome by Promoting Cd4+ T Cells' T Helper 17 Polarization","volume":"28","author":"Dong L. W.","year":"2022","journal-title":"World Journal of Gastroenterology"},{"issue":"1","key":"e_1_2_9_18_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1182\/blood-2013-02-482406","article-title":"Adenosine Production by Human B Cells and B Cell\u2010Mediated Suppression of Activated T Cells","volume":"122","author":"Saze Z.","year":"2013","journal-title":"Blood"},{"issue":"1","key":"e_1_2_9_19_1","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/s41467-022-28086-1","article-title":"Adenosine Receptor 2a Agonists Target Mouse Cd11c(+)T\u2010Bet(+) B Cells in Infection and Autoimmunity","volume":"13","author":"Levack R. C.","year":"2022","journal-title":"Nature Communications"},{"issue":"4","key":"e_1_2_9_20_1","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1111\/imm.13600","article-title":"Ahr\/Tet2\/Nt5e Axis Downregulation Is Associated With the Risk of Systemic Lupus Erythematosus and Its Progression","volume":"168","author":"Cheng H. 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L.","year":"2021","journal-title":"Arthritis Care & Research (Hoboken)"},{"key":"e_1_2_9_27_1","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2023.1258637","article-title":"Adenosine, Bridging Chronic Inflammation and Tumor Growth","volume":"14","author":"Chen L.","year":"2023","journal-title":"Frontiers in Immunology"},{"issue":"4","key":"e_1_2_9_28_1","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1111\/imm.70011","article-title":"Cd73 Expression by Cd4 (+) T Cells Marks Early Effector Memory T Cells","volume":"176","author":"Chen L.","year":"2025","journal-title":"Immunology"},{"issue":"10","key":"e_1_2_9_29_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.autrev.2025.103874","article-title":"Proportion of Circulating T Follicular Helper Cells in Peripheral Blood of Systemic Lupus Erythematosus Patients: A Systematic Review and Meta\u2010Analysis","volume":"24","author":"Feng F.","year":"2025","journal-title":"Autoimmunity 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Immunology"},{"issue":"9","key":"e_1_2_9_33_1","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1177\/09612033231189804","article-title":"Baffr Expression in Circulating T Follicular Helper (Cd4(+)Cxcr5(+)Pd\u20101(+)) And T Peripheral Helper (Cd4(+)Cxcr5(\u2212)Pd\u20101(+)) Cells in Systemic Lupus Erythematosus","volume":"32","author":"Sagrero\u2010Fabela N.","year":"2023","journal-title":"Lupus"},{"issue":"1","key":"e_1_2_9_34_1","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/s42003-024-05989-x","article-title":"Cytotoxic Tph Subset With Low B\u2010Cell Helper Functions and Its Involvement in Systemic Lupus Erythematosus","volume":"7","author":"Seki N.","year":"2024","journal-title":"Communications Biology"},{"issue":"11","key":"e_1_2_9_35_1","doi-asserted-by":"crossref","first-page":"2034","DOI":"10.1136\/ard.2009.124636","article-title":"Urinary T Cells in Active Lupus Nephritis Show an Effector Memory Phenotype","volume":"69","author":"Dolff S.","year":"2010","journal-title":"Annals of the Rheumatic Diseases"},{"issue":"1","key":"e_1_2_9_36_1","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/s42003-025-09431-8","article-title":"Single\u2010Cell Profiling Unveils Nephritis\u2010Related Circulating Immunological Signatures in Systemic Lupus Erythematosus Patients","volume":"9","author":"Liu Q.","year":"2026","journal-title":"Communications Biology"},{"issue":"4","key":"e_1_2_9_37_1","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1080\/25785826.2023.2202050","article-title":"Association of Il\u201017 Serum Levels With Clinical Findings and Systemic Lupus Erythematosus Disease Activity Index","volume":"46","author":"Ebrahimi Chaharom F.","year":"2023","journal-title":"Immunological Medicine"},{"key":"e_1_2_9_38_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2024.112743","article-title":"The Reduced Frequency of Cd39(+)Cd73(+) B Cell Subsets in Sle Patients Is Correlated With Disease Activity","volume":"140","author":"Dong K.","year":"2024","journal-title":"International Immunopharmacology"}],"container-title":["Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imm.70201","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/imm.70201","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imm.70201","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T02:05:07Z","timestamp":1789351507000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/imm.70201"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,13]]},"references-count":37,"alternative-id":["10.1111\/imm.70201"],"URL":"https:\/\/doi.org\/10.1111\/imm.70201","archive":["Portico"],"relation":{},"ISSN":["0019-2805","1365-2567"],"issn-type":[{"value":"0019-2805","type":"print"},{"value":"1365-2567","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,13]]},"assertion":[{"value":"2026-02-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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