{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T01:09:09Z","timestamp":1784596149836,"version":"3.55.0"},"reference-count":43,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T00:00:00Z","timestamp":1733011200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T00:00:00Z","timestamp":1733011200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T00:00:00Z","timestamp":1728259200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007921","name":"University of Pittsburgh","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007921","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"NIAID","doi-asserted-by":"publisher","award":["R01 AI097134"],"award-info":[{"award-number":["R01 AI097134"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.fr","clinicalkey.jp","clinicalkey.es","clinicalkey.com.au","clinicalkey.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Autoimmunity"],"published-print":{"date-parts":[[2024,12]]},"DOI":"10.1016\/j.jaut.2024.103324","type":"journal-article","created":{"date-parts":[[2024,10,13]],"date-time":"2024-10-13T19:36:15Z","timestamp":1728848175000},"page":"103324","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":5,"special_numbering":"C","title":["Unraveling the immunomodulatory impact of hydroxychloroquine on peripheral T cells using single-cell RNA sequencing"],"prefix":"10.1016","volume":"149","author":[{"given":"Huizhong","family":"Long","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Espinosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3884-962X","authenticated-orcid":false,"given":"Amr H.","family":"Sawalha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jaut.2024.103324_bib1","doi-asserted-by":"crossref","DOI":"10.15252\/emmm.202012476","article-title":"Hydroxychloroquine in rheumatic autoimmune disorders and beyond","volume":"12","author":"Nirk","year":"2020","journal-title":"EMBO Mol. Med."},{"key":"10.1016\/j.jaut.2024.103324_bib2","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/s41584-020-0372-x","article-title":"Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology","volume":"16","author":"Schrezenmeier","year":"2020","journal-title":"Nat. Rev. Rheumatol."},{"key":"10.1016\/j.jaut.2024.103324_bib3","doi-asserted-by":"crossref","DOI":"10.1177\/1759720X211073001","article-title":"Hydroxychloroquine in systemic lupus erythematosus: overview of current knowledge","volume":"14","author":"Dima","year":"2022","journal-title":"Ther Adv Musculoskelet Dis"},{"key":"10.1016\/j.jaut.2024.103324_bib4","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1136\/ard-2023-224762","article-title":"EULAR recommendations for the management of systemic lupus erythematosus: 2023 update","volume":"83","author":"Fanouriakis","year":"2024","journal-title":"Ann. Rheum. Dis."},{"key":"10.1016\/j.jaut.2024.103324_bib5","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1002\/acr.21664","article-title":"American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis","volume":"64","author":"Hahn","year":"2012","journal-title":"Arthritis Care Res."},{"key":"10.1016\/j.jaut.2024.103324_bib6","doi-asserted-by":"crossref","DOI":"10.1016\/j.jaut.2021.102707","article-title":"Guideline for the diagnosis, treatment and long-term management of cutaneous lupus erythematosus","volume":"123","author":"Lu","year":"2021","journal-title":"J. Autoimmun."},{"key":"10.1016\/j.jaut.2024.103324_bib7","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.1136\/annrheumdis-2012-202322","article-title":"Hydroxychloroquine in systemic lupus erythematosus: results of a French multicentre controlled trial (PLUS Study)","volume":"72","author":"Costedoat-Chalumeau","year":"2013","journal-title":"Ann. Rheum. Dis."},{"key":"10.1016\/j.jaut.2024.103324_bib8","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1002\/acr.25228","article-title":"Reference range of hydroxychloroquine blood levels that can reduce odds of active lupus and prevent flares","volume":"76","author":"Garg","year":"2024","journal-title":"Arthritis Care Res."},{"key":"10.1016\/j.jaut.2024.103324_bib9","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1002\/art.42645","article-title":"Association between severe nonadherence to hydroxychloroquine and systemic lupus erythematosus flares, damage, and mortality in 660 patients from the SLICC inception cohort","volume":"75","author":"Nguyen","year":"2023","journal-title":"Arthritis Rheumatol."},{"key":"10.1016\/j.jaut.2024.103324_bib10","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1080\/15548627.2018.1474314","article-title":"Chloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion","volume":"14","author":"Mauthe","year":"2018","journal-title":"Autophagy"},{"key":"10.1016\/j.jaut.2024.103324_bib11","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1093\/rheumatology\/kei282","article-title":"Chloroquine inhibits production of TNF-alpha, IL-1beta and IL-6 from lipopolysaccharide-stimulated human monocytes\/macrophages by different modes","volume":"45","author":"Jang","year":"2006","journal-title":"Rheumatology"},{"key":"10.1016\/j.jaut.2024.103324_bib12","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1186\/s13075-017-1393-y","article-title":"Hydroxychloroquine inhibits CD154 expression in CD4(+) T lymphocytes of systemic lupus erythematosus through NFAT, but not STAT5, signaling","volume":"19","author":"Wu","year":"2017","journal-title":"Arthritis Res. Ther."},{"key":"10.1016\/j.jaut.2024.103324_bib13","doi-asserted-by":"crossref","DOI":"10.1016\/j.isci.2021.103509","article-title":"Hydroxychloroquine inhibits the mitochondrial antioxidant system in activated T cells","volume":"24","author":"Kim","year":"2021","journal-title":"iScience"},{"key":"10.1016\/j.jaut.2024.103324_bib14","doi-asserted-by":"crossref","DOI":"10.1136\/lupus-2022-000841","article-title":"Hydroxychloroquine daily dose, hydroxychloroquine blood levels and the risk of flares in patients with systemic lupus erythematosus","volume":"10","author":"Fasano","year":"2023","journal-title":"Lupus Sci Med"},{"key":"10.1016\/j.jaut.2024.103324_bib15","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1186\/s13059-018-1603-1","article-title":"Cell Hashing with barcoded antibodies enables multiplexing and doublet detection for single cell genomics","volume":"19","author":"Stoeckius","year":"2018","journal-title":"Genome Biol."},{"key":"10.1016\/j.jaut.2024.103324_bib16","doi-asserted-by":"crossref","first-page":"3573","DOI":"10.1016\/j.cell.2021.04.048","article-title":"Integrated analysis of multimodal single-cell data","volume":"184","author":"Hao","year":"2021","journal-title":"Cell"},{"key":"10.1016\/j.jaut.2024.103324_bib17","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1038\/s41592-019-0619-0","article-title":"Fast, sensitive and accurate integration of single-cell data with Harmony","volume":"16","author":"Korsunsky","year":"2019","journal-title":"Nat. Methods"},{"key":"10.1016\/j.jaut.2024.103324_bib18","article-title":"clusterProfiler 4.0: a universal enrichment tool for interpreting omics data","volume":"2","author":"Wu","year":"2021","journal-title":"Innovation"},{"key":"10.1016\/j.jaut.2024.103324_bib19","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1038\/s41590-020-0743-0","article-title":"Mapping systemic lupus erythematosus heterogeneity at the single-cell level","volume":"21","author":"Nehar-Belaid","year":"2020","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.jaut.2024.103324_bib20","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1186\/s13059-015-0844-5","article-title":"MAST: a flexible statistical framework for assessing transcriptional changes and characterizing heterogeneity in single-cell RNA sequencing data","volume":"16","author":"Finak","year":"2015","journal-title":"Genome Biol."},{"key":"10.1016\/j.jaut.2024.103324_bib21","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1196\/annals.1422.005","article-title":"Blood concentrations of hydroxychloroquine and its desethyl derivative correlate negatively with the percentage of CD45RO+ cells among CD4+ lymphocytes in hydroxychloroquine-treated lupus patients","volume":"1108","author":"Sailler","year":"2007","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"10.1016\/j.jaut.2024.103324_bib22","doi-asserted-by":"crossref","first-page":"818","DOI":"10.3899\/jrheum.170737","article-title":"Hydroxychloroquine inhibits the differentiation of Th17 cells in systemic lupus erythematosus","volume":"45","author":"Yang","year":"2018","journal-title":"J. Rheumatol."},{"key":"10.1016\/j.jaut.2024.103324_bib23","doi-asserted-by":"crossref","first-page":"8051","DOI":"10.7150\/thno.43507","article-title":"Autophagy-lysosome inhibitor chloroquine prevents CTLA-4 degradation of T cells and attenuates acute rejection in murine skin and heart transplantation","volume":"10","author":"Cui","year":"2020","journal-title":"Theranostics"},{"key":"10.1016\/j.jaut.2024.103324_bib24","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1111\/j.1600-065X.2008.00639.x","article-title":"CTLA-4: a key regulatory point in the control of autoimmune disease","volume":"223","author":"Scalapino","year":"2008","journal-title":"Immunol. Rev."},{"key":"10.1016\/j.jaut.2024.103324_bib25","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1146\/annurev.immunol.19.1.225","article-title":"Complexities of CD28\/B7: CTLA-4 costimulatory pathways in autoimmunity and transplantation","volume":"19","author":"Salomon","year":"2001","journal-title":"Annu. Rev. Immunol."},{"key":"10.1016\/j.jaut.2024.103324_bib26","doi-asserted-by":"crossref","first-page":"13756","DOI":"10.1073\/pnas.0706509104","article-title":"Induction of autoimmune disease in CTLA-4-\/- mice depends on a specific CD28 motif that is required for in vivo costimulation","volume":"104","author":"Tai","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.jaut.2024.103324_bib27","doi-asserted-by":"crossref","first-page":"19396","DOI":"10.1073\/pnas.0806855105","article-title":"Defects in CTLA-4 are associated with abnormal regulatory T cell function in rheumatoid arthritis","volume":"105","author":"Flores-Borja","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.jaut.2024.103324_bib28","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/s00439-004-1244-1","article-title":"CTLA-4 polymorphisms and systemic lupus erythematosus (SLE): a meta-analysis","volume":"116","author":"Lee","year":"2005","journal-title":"Hum. Genet."},{"key":"10.1016\/j.jaut.2024.103324_bib29","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.jneuroim.2018.08.004","article-title":"CTLA-4, PD-1 and TIM-3 expression predominantly downregulated in MS patients","volume":"323","author":"Mohammadzadeh","year":"2018","journal-title":"J. Neuroimmunol."},{"key":"10.1016\/j.jaut.2024.103324_bib30","doi-asserted-by":"crossref","DOI":"10.1016\/j.cyto.2020.155119","article-title":"Low expressions of PD-L1 and CTLA-4 by induced CD4(+)CD25(+) Foxp3(+) Tregs in patients with SLE and their correlation with the disease activity","volume":"133","author":"Zhao","year":"2020","journal-title":"Cytokine"},{"key":"10.1016\/j.jaut.2024.103324_bib31","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1038\/ni.3172","article-title":"The ubiquitin-modifying enzyme A20 restricts ubiquitination of the kinase RIPK3 and protects cells from necroptosis","volume":"16","author":"Onizawa","year":"2015","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.jaut.2024.103324_bib32","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/nature13322","article-title":"Negative regulation of the NLRP3 inflammasome by A20 protects against arthritis","volume":"512","author":"Vande Walle","year":"2014","journal-title":"Nature"},{"key":"10.1016\/j.jaut.2024.103324_bib33","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/cmi.2009.3","article-title":"Cell death mechanisms induced by cytotoxic lymphocytes","volume":"6","author":"Chavez-Galan","year":"2009","journal-title":"Cell. Mol. Immunol."},{"key":"10.1016\/j.jaut.2024.103324_bib34","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1002\/art.39410","article-title":"Selective loss of signaling lymphocytic activation molecule family member 4-positive CD8+ T cells contributes to the decreased cytotoxic cell activity in systemic lupus erythematosus","volume":"68","author":"Kis-Toth","year":"2016","journal-title":"Arthritis Rheumatol."},{"key":"10.1016\/j.jaut.2024.103324_bib35","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1084\/jem.20051106","article-title":"Chloroquine enhances human CD8+ T cell responses against soluble antigens in vivo","volume":"202","author":"Accapezzato","year":"2005","journal-title":"J. Exp. Med."},{"key":"10.1016\/j.jaut.2024.103324_bib36","doi-asserted-by":"crossref","first-page":"3159","DOI":"10.1002\/eji.200838516","article-title":"FCRL6 distinguishes mature cytotoxic lymphocytes and is upregulated in patients with B-cell chronic lymphocytic leukemia","volume":"38","author":"Schreeder","year":"2008","journal-title":"Eur. J. Immunol."},{"key":"10.1016\/j.jaut.2024.103324_bib37","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejcb.2022.151242","article-title":"Roles of Hopx in the differentiation and functions of immune cells","volume":"101","author":"Bourque","year":"2022","journal-title":"Eur. J. Cell Biol."},{"key":"10.1016\/j.jaut.2024.103324_bib38","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1111\/ajt.12565","article-title":"Alloprimed CD8(+) T cells regulate alloantibody and eliminate alloprimed B cells through perforin- and FasL-dependent mechanisms","volume":"14","author":"Zimmerer","year":"2014","journal-title":"Am. J. Transplant."},{"key":"10.1016\/j.jaut.2024.103324_bib39","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1002\/art.40038","article-title":"Signaling lymphocytic activation molecule family member 7 engagement restores defective effector CD8+ T cell function in systemic lupus erythematosus","volume":"69","author":"Comte","year":"2017","journal-title":"Arthritis Rheumatol."},{"key":"10.1016\/j.jaut.2024.103324_bib40","doi-asserted-by":"crossref","first-page":"652","DOI":"10.4049\/jimmunol.160.2.652","article-title":"Perforin protects against autoimmunity in lupus-prone mice","volume":"160","author":"Peng","year":"1998","journal-title":"J. Immunol."},{"key":"10.1016\/j.jaut.2024.103324_bib41","doi-asserted-by":"crossref","first-page":"R39","DOI":"10.1172\/JCI8876","article-title":"Role of perforin in controlling B-cell hyperactivity and humoral autoimmunity","volume":"106","author":"Shustov","year":"2000","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.jaut.2024.103324_bib42","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.celrep.2019.12.014","article-title":"The CD38\/NAD\/SIRTUIN1\/EZH2 Axis mitigates cytotoxic CD8 T cell function and identifies patients with SLE prone to infections","volume":"30","author":"Katsuyama","year":"2020","journal-title":"Cell Rep."},{"key":"10.1016\/j.jaut.2024.103324_bib43","article-title":"CD38 reduces mitochondrial fitness and cytotoxic T cell response against viral infection in lupus patients by suppressing mitophagy","volume":"8","author":"Chen","year":"2022","journal-title":"Sci. Adv."}],"container-title":["Journal of Autoimmunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0896841124001586?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0896841124001586?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,2,2]],"date-time":"2025-02-02T11:41:17Z","timestamp":1738496477000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0896841124001586"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12]]},"references-count":43,"alternative-id":["S0896841124001586"],"URL":"https:\/\/doi.org\/10.1016\/j.jaut.2024.103324","relation":{},"ISSN":["0896-8411"],"issn-type":[{"value":"0896-8411","type":"print"}],"subject":[],"published":{"date-parts":[[2024,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Unraveling the immunomodulatory impact of hydroxychloroquine on peripheral T cells using single-cell RNA sequencing","name":"articletitle","label":"Article Title"},{"value":"Journal of Autoimmunity","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jaut.2024.103324","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 The Author(s). Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"103324"}}