Transcriptional Repressor HIC1 Contributes to Suppressive Function of Human Induced Regulatory T Cells

dc.contributorAalto-yliopistofi
dc.contributorAalto Universityen
dc.contributor.authorUbaid Ullah, Ullahen_US
dc.contributor.authorAndrabi, Syed Bilal Ahmaden_US
dc.contributor.authorTripathi, Subhash Kumaren_US
dc.contributor.authorDirasantha, Obaiahen_US
dc.contributor.authorKanduri, Kartieken_US
dc.contributor.authorRautio, Sinien_US
dc.contributor.authorGross, Catharina C.en_US
dc.contributor.authorLehtimäki, Sarien_US
dc.contributor.authorBala, Kanchanen_US
dc.contributor.authorTuomisto, Johannaen_US
dc.contributor.authorBhatia, Urvashien_US
dc.contributor.authorChakroborty, Deepankaren_US
dc.contributor.authorElo, Laura L.en_US
dc.contributor.authorLähdesmäki, Harrien_US
dc.contributor.authorWiendl, Heinzen_US
dc.contributor.authorRasool, Omiden_US
dc.contributor.authorLahesmaa, Riittaen_US
dc.contributor.departmentDepartment of Computer Scienceen
dc.contributor.groupauthorProfessorship Lähdesmäki Harrien
dc.contributor.groupauthorCentre of Excellence in Molecular Systems Immunology and Physiology Research Group, SyMMysen
dc.contributor.organizationÅbo Akademi Universityen_US
dc.contributor.organizationUniversity of Münsteren_US
dc.date.accessioned2018-04-04T09:38:39Z
dc.date.available2018-04-04T09:38:39Z
dc.date.issued2018-02-20en_US
dc.description.abstractRegulatory T (Treg) cells are critical in regulating the immune response. In vitro induced Treg (iTreg) cells have significant potential in clinical medicine. However, applying iTreg cells as therapeutics is complicated by the poor stability of human iTreg cells and their variable suppressive activity. Therefore, it is important to understand the molecular mechanisms of human iTreg cell specification. We identified hypermethylated in cancer 1 (HIC1) as a transcription factor upregulated early during the differentiation of human iTreg cells. Although FOXP3 expression was unaffected, HIC1 deficiency led to a considerable loss of suppression by iTreg cells with a concomitant increase in the expression of effector T cell associated genes. SNPs linked to several immune-mediated disorders were enriched around HIC1 binding sites, and in vitro binding assays indicated that these SNPs may alter the binding of HIC1. Our results suggest that HIC1 is an important contributor to iTreg cell development and function. Ullah et al. find that HIC1 is induced during human iTreg cell differentiation. HIC1 binds to and regulates the expression of key genes during iTreg differentiation. Several autoimmune-disease-associated SNPs are enriched near HIC1 ChIP-seq peaks.en
dc.description.versionPeer revieweden
dc.format.extent13
dc.format.extent2094-2106
dc.format.mimetypeapplication/pdfen_US
dc.identifier.citationUbaid Ullah, U, Andrabi, S B A, Tripathi, S K, Dirasantha, O, Kanduri, K, Rautio, S, Gross, C C, Lehtimäki, S, Bala, K, Tuomisto, J, Bhatia, U, Chakroborty, D, Elo, L L, Lähdesmäki, H, Wiendl, H, Rasool, O & Lahesmaa, R 2018, ' Transcriptional Repressor HIC1 Contributes to Suppressive Function of Human Induced Regulatory T Cells ', Cell Reports, vol. 22, no. 8, pp. 2094-2106 . https://doi.org/10.1016/j.celrep.2018.01.070en
dc.identifier.doi10.1016/j.celrep.2018.01.070en_US
dc.identifier.issn2211-1247
dc.identifier.otherPURE UUID: d946adda-9300-4a3c-88c9-08895ecc3d6fen_US
dc.identifier.otherPURE ITEMURL: https://research.aalto.fi/en/publications/d946adda-9300-4a3c-88c9-08895ecc3d6fen_US
dc.identifier.otherPURE LINK: http://www.scopus.com/inward/record.url?scp=85042194008&partnerID=8YFLogxKen_US
dc.identifier.otherPURE FILEURL: https://research.aalto.fi/files/18235277/1_s2.0_S2211124718301190_main.pdfen_US
dc.identifier.urihttps://aaltodoc.aalto.fi/handle/123456789/30606
dc.identifier.urnURN:NBN:fi:aalto-201804042069
dc.language.isoenen
dc.relation.ispartofseriesCell Reportsen
dc.relation.ispartofseriesVolume 22, issue 8en
dc.rightsopenAccessen
dc.subject.keywordChIP-seqen_US
dc.subject.keywordexpression kineticsen_US
dc.subject.keywordFOXP3en_US
dc.subject.keywordHIC1en_US
dc.subject.keywordiTregen_US
dc.subject.keywordregulatory SNPen_US
dc.subject.keywordRNA-seqen_US
dc.subject.keywordsuppressionen_US
dc.subject.keywordT cellsen_US
dc.subject.keywordtranscriptional regulationen_US
dc.titleTranscriptional Repressor HIC1 Contributes to Suppressive Function of Human Induced Regulatory T Cellsen
dc.typeA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessäfi
dc.type.versionpublishedVersion
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