Dr. Yiping is a associate director of Center for Applied Bioinformatics at St. Jude Children’s Research Hospital. His research interests include Bioinformatics method development and optimization, biomedical application of machine learning, epigenetic regulation of T-cell functions and cancer immunotherapy
|2020-||Associate Director||Gang Wu||St. Jude Children’s Research Hospital|
|2014-2019||Group Lead||Jinghui Zhang||St. Jude Children’s Research Hospital|
|2005-2014||Scientist/Senior scientist||Jinghui Zhang||St. Jude Children’s Research Hospital|
|2002-2005||Research Scientist||Diversa||Diversa Co|
T reg cells bearing a diverse antigen receptor repertoire suppress pathogenic T cells and maintain immune homeostasis during their long lifespan. How their robust function is determined genetically remains elusive. Here, we investigate the regulatory space of the cis-regulatory elements of T reg lineage–specifying factor Foxp3. Foxp3 enhancers are known as distinct readers of environmental cues controlling T reg cell induction or lineage stability. However, their single deficiencies cause mild, if any, immune dysregulation, leaving the key transcriptional mechanisms determining Foxp3 expression and thereby T reg cell suppressive capacity uncertain. We examined the collective activities of Foxp3 enhancers and found that they coordinate to maximize T reg cell induction, Foxp3 expression level, or lineage stability through distinct modes and that ablation of synergistic enhancers leads to lethal autoimmunity in young mice. Thus, the induction and maintenance of a diverse, stable T reg cell repertoire rely on combinatorial Foxp3 enhancers, suggesting broad, stage-specific, synergistic activities of cell-intrinsic factors and cell-extrinsic cues in determining T reg cell suppressive capacity.