期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 21, 期 18, 页码 -出版社
MDPI
DOI: 10.3390/ijms21186497
关键词
TCF1; WNT/beta catenin; T cell aging; T cell differentiation; memory T cells; T follicular helper cells; T cell exhaustion; stem-like CD8 T cells; immunosenescence
资金
- National Institutes of Health [R01 AR042527, R01 HL117913, R01 AI108906, R01 HL142068, P01 HL129941, R01 AI108891, R01 AG045779, U19 AI057266, R01 AI129191]
The transcription factor T cell factor 1 (TCF1), a pioneer transcription factor as well as a downstream effector of WNT/beta-catenin signaling, is indispensable for T cell development in the thymus. Recent studies have highlighted the additional critical role of TCF1 in peripheral T cell responses to acute and chronic infections as well as cancer. Here, we review the regulatory functions of TCF1 in the differentiation of T follicular helper cells, memory T cells and recently described stem-like exhausted T cells, where TCF1 promotes less differentiated stem-like cell states by controlling common gene-regulatory networks. These studies also provide insights into the mechanisms of defective T cell responses in older individuals. We discuss alterations in TCF1 expression and related regulatory networks with age and their consequences for T cell responses to infections and vaccination. The increasing understanding of the pathways regulating TCF1 expression and function in aged T cells holds the promise of enabling the design of therapeutic interventions aiming at improving T cell responses in older individuals.
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