General autoimmunity

Oral

Long Non-coding Rna and Methylome Profiles of Human Regulatory T Cells in Health and Disease

Friday, June 16
6:15 PM - 7:30 PM

Regulatory T cells (Tregs) play a pivotal role in regulating immune responses to self and foreign antigens. Recent findings highlighted that long-non-coding (lnc) RNAs control biological processes, acting as regulators of gene expression. We hypothesize that defects in lncRNA-dependent post-transcriptional or chromatin regulation in Tregs may affect gene expression resulting in altered Treg development, function or fitness in autoimmune and inflammatory disorders. Tregs (CD4+CD25+CD127low) and effector T (Teff) (CD4+CD25-CD127-/+) were purified by flow cytometry from the peripheral blood of healthy subjects (n=8) and the transcriptome and DNA-methylation profile were assessed. By RNA-Seq we identified 82 differentially expressed annotated lncRNAs in Tregs vs Teff (fdr2). A good proportion of the transcripts overlapped with CD4+ T-cell regulatory elements, Treg-associated coding genes, known FOXP3-binding sites, or are proximal to Treg-specific differentially methylated regions (DMRs), thus suggesting a function in the regulation of Treg biology. One of them hosts known autoimmune-disease associated single nucleotide polymorphisms. Preliminary data indicate that expression of Treg-specific lncRNAs is FOXP3-independent, since it is maintained in FOXP3-mutated Tregs from IPEX patients and is not induced upon ectopic over-expression of FOXP3 in CD4+ T cells. Together with known hypomethylated regions in Treg-associated genes, Medip-Seq analysis of the same samples identified a DMR in a previously not reported Treg-specific regulatory element proximal to the CTLA4-gene. We are currently investigating the functional relevance of Treg-specific lncRNAs and DMRs in Tregs from autoimmune patients. Our results will potentially enable the identification of novel targets to modulate Treg function in health and disease.

Rosalia Curto

Division of Regenerative Medicine Stem Cells and Gene Therapy, San Raffaele Telethon Institute for Gene Therapy, IRCSS San Raffaele Scientific Institute

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    Jose Garcia-Manteiga

    Centre for Translational Genomics and Bioinformatics (CTGB), IRCCS San Raffaele Scientific Institute

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      Giulia Barbiera

      Centre for Translational Genomics and Bioinformatics (CTGB), IRCCS San Raffaele Scientific Institute

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        Valeria Rossella

        Centre for Translational Genomics and Bioinformatics (CTGB), IRCCS San Raffaele Scientific Institute

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          Serenella Sartori

          Centre for Translational Genomics and Bioinformatics (CTGB), IRCCS San Raffaele Scientific Institute

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            Davide Cittaro

            Centre for Translational Genomics and Bioinformatics (CTGB), IRCCS San Raffaele Scientific Institute

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              Daniele Avancini

              Division of Regenerative Medicine Stem Cells and Gene Therapy, San Raffaele Telethon Institute for Gene Therapy, IRCSS San Raffaele Scientific Institute

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                Francesca Santoni de Sio

                Division of Regenerative Medicine Stem Cells and Gene Therapy, San Raffaele Telethon Institute for Gene Therapy, IRCSS San Raffaele Scientific Institute

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                  Rosa Bacchetta

                  Associate Professor
                  Department of Pediatrics, Division of Stem Cell Transplantation and Regenerative Medicine, Stanford University

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                    Silvia Gregori

                    Group Leader
                    San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), Division of Regenerative Medicine, Stem Cells and Gene Therapy

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                      Federica Barzaghi

                      Department of Paediatric Immunohematology, IRCCS San Raffaele Scientific Institute

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                        Laura Passerini

                        Division of Regenerative Medicine Stem Cells and Gene Therapy, San Raffaele Telethon Institute for Gene Therapy, IRCSS San Raffaele Scientific Institute

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                          Long Non-coding Rna and Methylome Profiles of Human Regulatory T Cells in Health and Disease



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