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  • Andrabi, Syed Bilal AhmadTurku Bioscience Centre, University of Turku and Åbo Akademi University, 20520, Turku, Finland; InFLAMES - Innovation Ecosystem Based on the Immune System Flagship University of Turku and Åbo Akademi University, 20520, Turku, Finland (författare)

Long noncoding RNA LIRIL2R modulates FOXP3 levels and suppressive function of human CD4+ regulatory T cells by regulating IL2RA

  • Artikel/kapitelEngelska2024

Förlag, utgivningsår, omfång ...

  • Proceedings of the National Academy of Sciences (PNAS),2024
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:oru-113972
  • https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-113972URI
  • https://doi.org/10.1073/pnas.2315363121DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Regulatory T cells (Tregs) are central in controlling immune responses, and dysregulation of their function can lead to autoimmune disorders or cancer. Despite extensive studies on Tregs, the basis of epigenetic regulation of human Treg development and function is incompletely understood. Long intergenic noncoding RNAs (lincRNA)s are important for shaping and maintaining the epigenetic landscape in different cell types. In this study, we identified a gene on the chromosome 6p25.3 locus, encoding a lincRNA, that was up-regulated during early differentiation of human Tregs. The lincRNA regulated the expression of interleukin-2 receptor alpha (IL2RA), and we named it the lincRNA regulator of IL2RA (LIRIL2R). Through transcriptomics, epigenomics, and proteomics analysis of LIRIL2R-deficient Tregs, coupled with global profiling of LIRIL2R binding sites using chromatin isolation by RNA purification, followed by sequencing, we identified IL2RA as a target of LIRIL2R. This nuclear lincRNA binds upstream of the IL2RA locus and regulates its epigenetic landscape and transcription. CRISPR-mediated deletion of the LIRIL2R-bound region at the IL2RA locus resulted in reduced IL2RA expression. Notably, LIRIL2R deficiency led to reduced expression of Treg-signature genes (e.g., FOXP3, CTLA4, and PDCD1), upregulation of genes associated with effector T cells (e.g., SATB1 and GATA3), and loss of Treg-mediated suppression.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Kalim, Ubaid UllahTurku Bioscience Centre, University of Turku and Åbo Akademi University, 20520, Turku, Finland; InFLAMES - Innovation Ecosystem Based on the Immune System Flagship University of Turku and Åbo Akademi University, 20520, Turku, Finland (författare)
  • Palani, SenthilTurku Bioscience Centre, University of Turku and Åbo Akademi University, 20520, Turku, Finland (författare)
  • Khan, Mohd MoinTurku Bioscience Centre, University of Turku and Åbo Akademi University, 20520, Turku, Finland; InFLAMES - Innovation Ecosystem Based on the Immune System Flagship University of Turku and Åbo Akademi University, 20520, Turku, Finland (författare)
  • Khan, Meraj HasanTurku Bioscience Centre, University of Turku and Åbo Akademi University, 20520, Turku, Finland; InFLAMES - Innovation Ecosystem Based on the Immune System Flagship University of Turku and Åbo Akademi University, 20520, Turku, Finland (författare)
  • Fagersund, JimmyTurku Bioscience Centre, University of Turku and Åbo Akademi University, 20520, Turku, Finland; InFLAMES - Innovation Ecosystem Based on the Immune System Flagship University of Turku and Åbo Akademi University, 20520, Turku, Finland (författare)
  • Orpana, JuliusTurku Bioscience Centre, University of Turku and Åbo Akademi University, 20520, Turku, Finland; InFLAMES - Innovation Ecosystem Based on the Immune System Flagship University of Turku and Åbo Akademi University, 20520, Turku, Finland (författare)
  • Paulin, NiklasTurku Bioscience Centre, University of Turku and Åbo Akademi University, 20520, Turku, Finland; InFLAMES - Innovation Ecosystem Based on the Immune System Flagship University of Turku and Åbo Akademi University, 20520, Turku, Finland (författare)
  • Batkulwar, KedarTurku Bioscience Centre, University of Turku and Åbo Akademi University, 20520, Turku, Finland; InFLAMES - Innovation Ecosystem Based on the Immune System Flagship University of Turku and Åbo Akademi University, 20520, Turku, Finland (författare)
  • Junttila, SiniTurku Bioscience Centre, University of Turku and Åbo Akademi University, 20520, Turku, Finland; InFLAMES - Innovation Ecosystem Based on the Immune System Flagship University of Turku and Åbo Akademi University, 20520, Turku, Finland (författare)
  • Buchacher, TanjaTurku Bioscience Centre, University of Turku and Åbo Akademi University, 20520, Turku, Finland; InFLAMES - Innovation Ecosystem Based on the Immune System Flagship University of Turku and Åbo Akademi University, 20520, Turku, Finland (författare)
  • Grönroos, ToniTurku Bioscience Centre, University of Turku and Åbo Akademi University, 20520, Turku, Finland (författare)
  • Toikka, LeaTurku Bioscience Centre, University of Turku and Åbo Akademi University, 20520, Turku, Finland (författare)
  • Ammunet, TeaTurku Bioscience Centre, University of Turku and Åbo Akademi University, 20520, Turku, Finland; InFLAMES - Innovation Ecosystem Based on the Immune System Flagship University of Turku and Åbo Akademi University, 20520, Turku, Finland (författare)
  • Sen, ParthoTurku Bioscience Centre, University of Turku and Åbo Akademi University, 20520, Turku, Finland (författare)
  • Oresic, Matej,1967-Örebro universitet,Institutionen för medicinska vetenskaper,Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520, Turku, Finland; InFLAMES - Innovation Ecosystem Based on the Immune System Flagship University of Turku and Åbo Akademi University, 20520, Turku, Finland(Swepub:oru)moc (författare)
  • Kumpulainen, VenlaTurku Bioscience Centre, University of Turku and Åbo Akademi University, 20520, Turku, Finland (författare)
  • Tuomisto, Johanna E. E.Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520, Turku, Finland (författare)
  • Sinha, RahulInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA, USA (författare)
  • Marson, AlexanderGladstone-University of California San Francisco Institute of Genomic Immunology, San Francisco, CA, USA (författare)
  • Rasool, OmidTurku Bioscience Centre, University of Turku and Åbo Akademi University, 20520, Turku, Finland; InFLAMES - Innovation Ecosystem Based on the Immune System Flagship University of Turku and Åbo Akademi University, 20520, Turku, Finland (författare)
  • Elo, Laura L.Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520, Turku, Finland; InFLAMES - Innovation Ecosystem Based on the Immune System Flagship University of Turku and Åbo Akademi University, 20520, Turku, Finland; Institute of Biomedicine, University of Turku, 20520 Turku, Finland (författare)
  • Lahesmaa, RiittaTurku Bioscience Centre, University of Turku and Åbo Akademi University, 20520, Turku, Finland; InFLAMES - Innovation Ecosystem Based on the Immune System Flagship University of Turku and Åbo Akademi University, 20520, Turku, Finland; Institute of Biomedicine, University of Turku, 20520 Turku, Finland (författare)
  • Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520, Turku, Finland; InFLAMES - Innovation Ecosystem Based on the Immune System Flagship University of Turku and Åbo Akademi University, 20520, Turku, FinlandTurku Bioscience Centre, University of Turku and Åbo Akademi University, 20520, Turku, Finland (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Proceedings of the National Academy of Sciences of the United States of America: Proceedings of the National Academy of Sciences (PNAS)121:230027-84241091-6490

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