{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T05:14:50Z","timestamp":1780463690741,"version":"3.54.1"},"reference-count":126,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,5,26]],"date-time":"2021-05-26T00:00:00Z","timestamp":1621987200000},"content-version":"vor","delay-in-days":145,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin &amp;amp; Trans Imm"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Regulatory T cells (Tregs) are widely recognised as a subset of CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup>FOXP3<jats:sup>+<\/jats:sup> T cells that have a key role in maintaining immune homeostasis. The impact of HIV\u20101 infection on immunological properties and effector functions of Tregs has remained the topic of debate and controversy. In the present study, we investigated transcriptional profile and functional properties of Tregs in HIV\u20101\u2010infected individuals either receiving antiretroviral therapy (ART, <jats:italic>n<\/jats:italic>\u00a0=\u00a050) or long\u2010term non\u2010progressors (LTNPs, <jats:italic>n<\/jats:italic>\u00a0=\u00a024) compared to healthy controls (HCs, <jats:italic>n<\/jats:italic>\u00a0=\u00a038).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>RNA sequencing (RNAseq), flow cytometry\u2010based immunophenotyping and functional assays were performed to study Tregs in different HIV cohorts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our RNAseq analysis revealed that Tregs exhibit different transcriptional profiles in HIV\u2010infected individuals. While Tregs from patients on ART upregulate pathways associated with a more suppressive (activated) phenotype, Tregs in LTNPs exhibit upregulation of pathways associated with impaired suppressive properties. These observations may explain a higher propensity for autoimmune diseases in LTNPs. Also, we found substantial upregulation of HLA\u2010F mRNA and HLA\u2010F protein in Tregs from HIV\u2010infected subjects compared to healthy individuals. These observations highlight a potential role for this non\u2010classical HLA in Tregs in the context of HIV infection, which should be investigated further in other chronic viral infections and cancer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study has provided a novel insight into Tregs at the transcriptional and functional levels in different HIV\u2010infected groups.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cti2.1289","type":"journal-article","created":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T06:27:56Z","timestamp":1622096876000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Differential transcriptional and functional properties of regulatory T cells in HIV\u2010infected individuals on antiretroviral therapy and long\u2010term non\u2010progressors"],"prefix":"10.1002","volume":"10","author":[{"given":"Shima","family":"Shahbaz","sequence":"first","affiliation":[{"name":"School of Dentistry Faculty of Medicine and Dentistry University of Alberta  Edmonton AB Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Jovel","sequence":"additional","affiliation":[{"name":"School of Dentistry Faculty of Medicine and Dentistry University of Alberta  Edmonton AB Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7215-2009","authenticated-orcid":false,"given":"Shokrollah","family":"Elahi","sequence":"additional","affiliation":[{"name":"School of Dentistry Faculty of Medicine and Dentistry University of Alberta  Edmonton AB Canada"},{"name":"Department of Medical Microbiology and Immunology Faculty of Medicine and Dentistry University of Alberta  Edmonton AB Canada"},{"name":"Department of Oncology Faculty of Medicine and Dentistry University of Alberta  Edmonton AB Canada"},{"name":"Li Ka Shing Institute of Virology Faculty of Medicine and Dentistry University of Alberta  Edmonton AB Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,5,26]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0000000000000917"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e328337b957"},{"key":"e_1_2_9_4_1","first-page":"223","article-title":"Endothelial dysfunction in HIV infection\u2013the role of circulating endothelial cells, microparticles, endothelial progenitor cells and macrophages","volume":"14","author":"L\u00f3pez M","year":"2012","journal-title":"AIDS Rev"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-11-389585"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.5.2454-2459.2004"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.21.120601.141122"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1079490"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.04.010"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOT.0000000000000212"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.1.301"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2017.388"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2012.05.003"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2422"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.54.101601.152346"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1008696"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2008.02978.x"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0015924"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.05608-11"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-07-409755"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0020198"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.2.764"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00249-06"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601881"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-019-03649-x"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2001.4971"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2018.01.011"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1152725"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.23309"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/0959-440X(95)80014-R"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.9.4666-4670.2002"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(86)90532-5"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.2A0618-228R"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4690-9-33"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M704410200"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01384-08"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.1999.00917.x"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00832"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201040348"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12297"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1701477"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.2217\/imt.14.84"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2012.01152.x"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI130426"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.08.068"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.8.4622"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01758-10"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.08-120550"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.08-108043"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3390"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2091-3-11"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(03)00268-1"},{"key":"e_1_2_9_53_1","first-page":"713","article-title":"Activation of Akt\u2010mTOR\u2010p70S6K pathway in angiogenesis in hepatocellular carcinoma","volume":"20","author":"Li W","year":"2008","journal-title":"Oncol Rep"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.069070"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.10.010"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.668442"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3004"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3540"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0291-z"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-07-232694"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.7.2.5312"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V114.22.4088.4088"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.03.018"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep24249"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2017.05.012"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02716"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3577"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19061575"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-230X-10-60"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.5.2940"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.7.4129"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(04)00030-5"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8140422"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.4161\/jkst.24529"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.05.027"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2009.05.007"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.4161\/hv.20203"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.12467"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1002691"},{"key":"e_1_2_9_80_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201041205"},{"key":"e_1_2_9_81_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1500036"},{"key":"e_1_2_9_82_1","doi-asserted-by":"publisher","DOI":"10.5411\/wji.v4.i2.63"},{"key":"e_1_2_9_83_1","doi-asserted-by":"publisher","DOI":"10.1089\/vim.2015.0062"},{"key":"e_1_2_9_84_1","doi-asserted-by":"crossref","first-page":"188.10","DOI":"10.4049\/jimmunol.190.Supp.188.10","article-title":"Regulatory T cells mediate immunosuppression induced by experimental hypothyroidism (P1215)","volume":"190","author":"Valli E","year":"2013","journal-title":"J Immunol"},{"key":"e_1_2_9_85_1","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2015.72"},{"key":"e_1_2_9_86_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3868"},{"key":"e_1_2_9_87_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2009.16"},{"key":"e_1_2_9_88_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2008.167"},{"key":"e_1_2_9_89_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0113018"},{"key":"e_1_2_9_90_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01578"},{"key":"e_1_2_9_91_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiu188"},{"key":"e_1_2_9_92_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e32836253fd"},{"key":"e_1_2_9_93_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.7.4407"},{"key":"e_1_2_9_94_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20032069"},{"key":"e_1_2_9_95_1","doi-asserted-by":"publisher","DOI":"10.1089\/aid.2006.0162"},{"key":"e_1_2_9_96_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04392-5"},{"key":"e_1_2_9_97_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2016.26"},{"key":"e_1_2_9_98_1","doi-asserted-by":"publisher","DOI":"10.1111\/imm.13178"},{"key":"e_1_2_9_99_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07674"},{"key":"e_1_2_9_100_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.274027.115"},{"key":"e_1_2_9_101_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-02-207118"},{"key":"e_1_2_9_102_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0700298104"},{"key":"e_1_2_9_103_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.19.11059"},{"key":"e_1_2_9_104_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20070419"},{"key":"e_1_2_9_105_1","doi-asserted-by":"publisher","DOI":"10.3109\/10409238.2016.1143913"},{"key":"e_1_2_9_106_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1600691"},{"key":"e_1_2_9_107_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0402874101"},{"key":"e_1_2_9_108_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0801792"},{"key":"e_1_2_9_109_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.07.033"},{"key":"e_1_2_9_110_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00204.2015"},{"key":"e_1_2_9_111_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02839"},{"key":"e_1_2_9_112_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3365"},{"key":"e_1_2_9_113_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02839"},{"key":"e_1_2_9_114_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.12.018"},{"key":"e_1_2_9_115_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13306"},{"key":"e_1_2_9_116_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.14-268409"},{"key":"e_1_2_9_117_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05676-6"},{"key":"e_1_2_9_118_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-378630-2.00040-2"},{"key":"e_1_2_9_119_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-017-0002-2"},{"key":"e_1_2_9_120_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.11.6464"},{"key":"e_1_2_9_121_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3513"},{"key":"e_1_2_9_122_1","doi-asserted-by":"publisher","DOI":"10.1089\/1050725041517048"},{"key":"e_1_2_9_123_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1901481"},{"key":"e_1_2_9_124_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1700742"},{"key":"e_1_2_9_125_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.2006649"},{"key":"e_1_2_9_126_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3519"},{"key":"e_1_2_9_127_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"}],"container-title":["Clinical &amp; Translational Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cti2.1289","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cti2.1289","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cti2.1289","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T19:27:28Z","timestamp":1693596448000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cti2.1289"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1]]},"references-count":126,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2021,1]]}},"alternative-id":["10.1002\/cti2.1289"],"URL":"https:\/\/doi.org\/10.1002\/cti2.1289","archive":["Portico"],"relation":{},"ISSN":["2050-0068","2050-0068"],"issn-type":[{"value":"2050-0068","type":"print"},{"value":"2050-0068","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1]]},"assertion":[{"value":"2021-01-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-04-29","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e1289"}}