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Transcriptional and Epigenetic Regulation of Context-Dependent Plasticity in T-Helper Lineages

  • Meyer J. Friedman (Department and School of Medicine, University of California) ;
  • Haram Lee (College of Pharmacy Korea University) ;
  • June-Yong Lee (Department of Microbiology and Immunology, Yonsei University College of Medicine) ;
  • Soohwan Oh (College of Pharmacy Korea University)
  • Received : 2023.01.01
  • Accepted : 2023.02.13
  • Published : 2023.02.28
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Abstract

Th cell lineage determination and functional specialization are tightly linked to the activation of lineage-determining transcription factors (TFs) that bind cis-regulatory elements. These lineage-determining TFs act in concert with multiple layers of transcriptional regulators to alter the epigenetic landscape, including DNA methylation, histone modification and threedimensional chromosome architecture, in order to facilitate the specific Th gene expression programs that allow for phenotypic diversification. Accumulating evidence indicates that Th cell differentiation is not as rigid as classically held; rather, extensive phenotypic plasticity is an inherent feature of T cell lineages. Recent studies have begun to uncover the epigenetic programs that mechanistically govern T cell subset specification and immunological memory. Advances in next generation sequencing technologies have allowed global transcriptomic and epigenomic interrogation of CD4+ Th cells that extends previous findings focusing on individual loci. In this review, we provide an overview of recent genome-wide insights into the transcriptional and epigenetic regulation of CD4+ T cell-mediated adaptive immunity and discuss the implications for disease as well as immunotherapies.

Keywords

Acknowledgement

June-Yong Lee is supported by a faculty research grant of Yonsei University College of Medicine (6-2022-0119), a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HV22C024901), and the Ministry of Education of the Republic of Korea and the National Research Foundation of Korea (2021R1C1C100691212). Soohwan Oh is supported by a Korea University Grant and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2022R1C1C101069911) and faculty research grant of Korea University (K2223251). Figures have been created with BioRender.

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