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Updated: Jun 25, 2025
08:20
In Vitro Differentiation of Human CD4+FOXP3+ Induced Regulatory T Cells (iTregs) from Naïve CD4+ T Cells Using a TGF-β-containing Protocol
Published on: December 30, 2016
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Long noncoding RNA LIRIL2R modulates FOXP3 levels and suppressive function of human CD4+ regulatory T cells by
Syed Bilal Ahmad Andrabi1,2, Ubaid Ullah Kalim1,2, Senthil Palani1
1Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520, Turku, Finland.
Summary
A newly discovered long intergenic noncoding RNA, LIRIL2R, is crucial for regulating human regulatory T cell (Treg) function. LIRIL2R controls IL2RA expression and Treg-specific gene activity, impacting immune responses.
Area of Science:
- Immunology
- Epigenetics
- Molecular Biology
Background:
- Regulatory T cells (Tregs) are critical for immune homeostasis, and their dysfunction is implicated in autoimmunity and cancer.
- Epigenetic regulation of human Treg development and function remains incompletely understood.
- Long intergenic noncoding RNAs (lincRNAs) play a role in epigenetic regulation.
Purpose of the Study:
- To identify and characterize a novel lincRNA involved in human Treg differentiation and function.
- To elucidate the mechanism by which this lincRNA regulates the interleukin-2 receptor alpha (IL2RA) gene.
- To investigate the impact of this lincRNA on Treg-specific gene expression and suppressive capacity.
Main Methods:
- Identification of a novel lincRNA (LIRIL2R) upregulated during human Treg differentiation.
- Transcriptomics, epigenomics, and proteomics analysis of LIRIL2R-deficient Tregs.
- Chromatin isolation by RNA purification followed by sequencing (ChIRP-seq) to map LIRIL2R binding sites.
- CRISPR-mediated deletion of the LIRIL2R binding region at the IL2RA locus.
Main Results:
- LIRIL2R was identified as a nuclear lincRNA binding upstream of the IL2RA locus, regulating its epigenetic landscape and transcription.
- CRISPR-mediated deletion of the LIRIL2R binding site reduced IL2RA expression.
- LIRIL2R deficiency resulted in decreased expression of Treg-signature genes (FOXP3, CTLA4, PDCD1) and increased expression of effector T cell genes (SATB1, GATA3).
- Loss of LIRIL2R led to impaired Treg-mediated suppression.
Conclusions:
- LIRIL2R is a key epigenetic regulator of human Treg development and function.
- LIRIL2R controls Treg identity and suppressive function through regulation of IL2RA and other Treg-specific genes.
- LIRIL2R represents a potential therapeutic target for immune-related disorders.
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