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  UPCOMING EVENTS   Selected Seminar        
     
 
Date: 1 March 2018
Time: 11:00am | Level 3, IMCB Seminar Room 3-46, Proteos
Speaker: Dr. Melissa Ng
Title: Helios primes human fetal naïve T cells for preferential regulatory T cell differentiation


Human fetal CD4+ naïve T cells preferentially differentiate into CD25hiFOXP3hi regulatory T (Treg) cells upon T cell receptor (TCR) stimulation without requiring addition TGFβ supplementation, thus contributing to the generation of immunotolerance in utero. Alongside expression of the lineage-determining factor FOXP3, commitment to the Treg cell fate is preceded by the acquisition of permissive epigenetic modifications at Treg-specific enhancers associated with the transcriptional control of Treg signature genes. We show using ATACseq (Assay for Transposase-Accessible Chromatin Sequencing) and H3K27ac ChIPseq (Chromatin Immunoprecipitation Sequencing) that fetal naïve T cells have increased chromatin accessibility and H3K27ac enrichment at a subset of Treg-associated enhancers. Fetal naïve T cells subsequently have increased transcription of the underlying Treg-associated genes such as Helios (IKZF2). Using flow cytometry, we confirmed that Helios expression is higher in fetal naïve T cells relative to adult naïve T cells. CRISPR (clustered regular interspaced short palindromic repeats)-Cas9 (CRISPR-associated protein 9) mediated knockdown of Helios expression in primary fetal naïve T cells inhibited this intrinsic ability for CD25hiFOXP3hi Treg differentiation, indicating that high baseline Helios expression contributes to the priming of Treg differentiation in fetal naïve T cells. Overall, a novel Treg-associated epigenome and transcriptome within fetal naïve T cells establishes preferential Treg differentiation as a mechanism to maintain immunotolerance in utero.

Biography:
Melissa Ng is a 5th Year Ph.D. Candidate in the Biomedical Sciences Graduate Program at the University of California, San Francisco (UCSF), and an A*STAR NSS (Ph.D.) Scholar. Her work focuses on the immunology of the developing human immune system, with an interest in how immune tolerance is maintained in the human fetus by regulatory T cells. Her dissertion explores the epigenetic mechanisms by which fetal naïve T cells are primed for preferential regulatory T cell differentiation, and how the subsequent expression of genes such as Helios contributes to this process. She is currently investigating how to recreate this ability in adult naïve T cells with the long-term goal of making better regulatory T cells for immunotherapy.


Host: Prof. Vinay Tergaonkar

 

Seminar is open to public, registration is not required.

 
     

 
 
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