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β-Catenin/TCF-1 Pathway in T Cell Development and Differentiation

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Abstract

T cells must undergo two critical differentiation processes before they become competent effectors that can mediate actual immune responses. Progenitor T cells undergo defined stages of differentiation in the thymus, which include positive and negative selection, to generate a repertoire of T cells that will respond to foreign but not self antigens. When these immunocompetent T cells first migrate out of thymus into peripheral lymphoid tissues, they are naïve and are unable to mediate immune responses. However, upon antigen encounter, peripheral CD4+ naïve T cells undergo another differentiation process to become armed effector T cells including Th1, Th2, Th17 or regulatory T cells, all of which are capable of regulating immune responses. A canonical Wnt/β-catenin/T cell factor (TCF) pathway has been shown to regulate T cell differentiation in both the thymus and in peripheral lymphoid tissues. Dysfunction of this pathway at any stage of T cell differentiation could lead to severe autoimmunity including experimental autoimmune encephalomyelitis or immune deficiency. Understanding the role played by β-catenin/TCF-1 in T cell differentiation will facilitate our understanding of the mechanisms that regulate T cell function and assist in identifying novel therapy targets for treating both autoimmune and immune diseases. Therefore, in this review, we will focus on the function of β-catenin/TCF-1 pathway in the regulation of thymic and peripheral T cell differentiation processes.

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Acknowledgments

We thank Dr. Margaret Morgan for expert editorial assistance.

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Correspondence to Zuoming Sun.

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Our work was supported by grants NIH R01-AI053147, NIH R56-AI072554, the Nesvig lymphoma Fellowship and Research Fund and City of Hope.

Authors of the paper have no financial conflict of interests in connection this manuscript.

Jian Ma and Ruiqing Wang contributed equally.

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Ma, J., Wang, R., Fang, X. et al. β-Catenin/TCF-1 Pathway in T Cell Development and Differentiation. J Neuroimmune Pharmacol 7, 750–762 (2012). https://doi.org/10.1007/s11481-012-9367-y

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