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TCF-1: a maverick in T cell development and function

Nature Immunology volume 23, pages 671–678 (2022)Cite this article

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Abstract

The T cell-specific DNA-binding protein TCF-1 is a central regulator of T cell development and function along multiple stages and lineages. Because it interacts with β-catenin, TCF-1 has been classically viewed as a downstream effector of canonical Wnt signaling, although there is strong evidence for β-catenin-independent TCF-1 functions. TCF-1 co-binds accessible regulatory regions containing or lacking its conserved motif and cooperates with other nuclear factors to establish context-dependent epigenetic and transcription programs that are essential for T cell development and for regulating immune responses to infection, autoimmunity and cancer. Although it has mostly been associated with positive regulation of chromatin accessibility and gene expression, TCF-1 has the potential to reduce chromatin accessibility and thereby suppress gene expression. In addition, the binding of TCF-1 bends the DNA and affects the chromatin conformation genome wide. This Review discusses the current understanding of the multiple roles of TCF-1 in T cell development and function and their mechanistic underpinnings.

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Fig. 1: T cell development and the stages of TCF-1 implication.
Fig. 2: Understanding the fundamental molecular functions of TCF-1.

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Acknowledgements

This work was supported by US National Institutes of Health grants R01 AI 108682 (to F.G. and K.K.) and R01 AI 147652 (to F.G.).

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  1. Knapp Research Center, Section of Rheumatology, Department of Medicine, University of Chicago, Chicago, IL, USA

    Fotini Gounari

  2. Department of Immunology, Mayo Clinic, Scottsdale, AZ, USA

    Fotini Gounari & Khashayarsha Khazaie

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Gounari, F., Khazaie, K. TCF-1: a maverick in T cell development and function. Nat Immunol 23, 671–678 (2022). https://doi.org/10.1038/s41590-022-01194-2

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