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ZBTB Transcription Factors: Key Regulators of the Development, Differentiation and Effector Function of T Cells

Journal

FRONTIERS IN IMMUNOLOGY
Volume 12, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.713294

Keywords

thymic T-cell development; T-cell differentiation; T-cell effector function; ZBTB proteins; transcriptional regulation

Categories

Funding

  1. National Key Research and Development Program of China [2017YFA0104502]
  2. National Natural Science Foundation of China [31670888/81970371/81470564]
  3. Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)

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The development and differentiation of T cells is regulated by various transcription factors, with ZBTB family members playing critical roles in both conventional and unconventional T cell lineages, influencing the development, differentiation, and effector function of these cells.
The development and differentiation of T cells represents a long and highly coordinated, yet flexible at some points, pathway, along which the sequential and dynamic expressions of different transcriptional factors play prominent roles at multiple steps. The large ZBTB family comprises a diverse group of transcriptional factors, and many of them have emerged as critical factors that regulate the lineage commitment, differentiation and effector function of hematopoietic-derived cells as well as a variety of other developmental events. Within the T-cell lineage, several ZBTB proteins, including ZBTB1, ZBTB17, ZBTB7B (THPOK) and BCL6 (ZBTB27), mainly regulate the development and/or differentiation of conventional CD4/CD8 alpha beta(+) T cells, whereas ZBTB16 (PLZF) is essential for the development and function of innate-like unconventional gamma delta(+) T & invariant NKT cells. Given the critical role of T cells in host defenses against infections/tumors and in the pathogenesis of many inflammatory disorders, we herein summarize the roles of fourteen ZBTB family members in the development, differentiation and effector function of both conventional and unconventional T cells as well as the underlying molecular mechanisms.

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