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

Andrabi, Syed Bilal Ahmad (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, Finland
Kalim, Ubaid Ullah (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, Finland
Palani, Senthil (författare)
Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520, Turku, Finland
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Khan, Mohd Moin (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, Finland
Khan, Meraj Hasan (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, Finland
Fagersund, Jimmy (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, Finland
Orpana, Julius (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, Finland
Paulin, Niklas (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, Finland
Batkulwar, Kedar (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, Finland
Junttila, Sini (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, Finland
Buchacher, Tanja (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, Finland
Grönroos, Toni (författare)
Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520, Turku, Finland
Toikka, Lea (författare)
Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520, Turku, Finland
Ammunet, Tea (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, Finland
Sen, Partho (författare)
Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520, Turku, Finland
Oresic, Matej, 1967- (författare)
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
Kumpulainen, Venla (författare)
Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520, Turku, Finland
Tuomisto, Johanna E. E. (författare)
Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520, Turku, Finland
Sinha, Rahul (författare)
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA, USA
Marson, Alexander (författare)
Gladstone-University of California San Francisco Institute of Genomic Immunology, San Francisco, CA, USA
Rasool, Omid (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, Finland
Elo, Laura L. (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, Finland; Institute of Biomedicine, University of Turku, 20520 Turku, Finland
Lahesmaa, Riitta (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, Finland; Institute of Biomedicine, University of Turku, 20520 Turku, Finland
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 (creator_code:org_t)
Proceedings of the National Academy of Sciences (PNAS), 2024
2024
Engelska.
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 121:23
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • 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

NATURVETENSKAP  -- Biologi -- Cellbiologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Cell Biology (hsv//eng)

Nyckelord

FOXP3
IL2RA
LIRIL2R
long noncoding RNA
regulatory T cells

Publikations- och innehållstyp

ref (ämneskategori)
art (ämneskategori)

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