The Transcription Factor TCF1 in T Cell Differentiation and Aging

Kim, Chulwoo; Jin, Jun; Weyand, Cornelia M.; Goronzy, Jörg J.

doi:10.3390/ijms21186497

Cited by 59 publications

(48 citation statements)

References 124 publications

(207 reference statements)

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“…Immunosenescence interferes with T cell function and differentiation, assessed by flow cytometry and T cell receptors. The resulting alterations in T cell phenotype modify both rejection and tolerance [67]. Future studies are required to assess the impacts of immunosenescence and inflamm-aging in older kidney transplant recipients on tolerance induction, rejection, infection, and malignancy.…”

Section: Immune Changes With Aging: Immunosenescencementioning

confidence: 99%

Immunosuppression Considerations for Older Kidney Transplant Recipients

et al. 2021

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Purpose of Review While kidney transplantation improves the long-term survival of the majority of patients with end-stage kidney disease (ESKD), age-related immune dysfunction and associated comorbidities make older transplant recipients more susceptible to complications related to immunosuppression. In this review, we discuss appropriate management of immunosuppressive agents in older adults to minimize adverse events, avoid acute rejection, and maximize patient and graft survival. Recent Findings Physiological changes associated with senescence can impact drug metabolism and increase the risk of post-transplant infection and malignancy. Clinical trials assessing the safety and efficacy of immunosuppressive agents in older adults are lacking. Recent findings from U.S. transplant registry–based studies suggest that risk-adjusted death-censored graft failure is higher among older patients who received antimetabolite avoidance, mammalian target of rapamycin inhibitor (mTORi)–based, and cyclosporine-based regimens. Observational data suggest that risk-adjusted mortality may be increased in older patients who receive mTORi-based and cyclosporine-based regimens but lower in those managed with T cell induction and maintenance steroid avoidance/withdrawal. Summary Tailored immunosuppression management to improve patient and graft survival in older transplant recipients is an important goal of personalized medicine. Lower intensity immunosuppression, such as steroid-sparing regimens, appears beneficial whereas mTORi- and cyclosporine-based maintenance are associated with greater potential for adverse effects. Prospective clinical trials to assess the safety and efficacy of immunosuppression agents in older recipients are urgently needed.

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Section: Immune Changes With Aging: Immunosenescencementioning

confidence: 99%

Immunosuppression Considerations for Older Kidney Transplant Recipients

et al. 2021

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“…Given that over 70% of cancers occur in individuals over the age of 50, the gradual loss of TCF1 expression amongst the host immune cells may cause a reduction in the ability of the host to properly respond against and clear new neoplasms [ 31 ]. Thus, TCF1 may be a major determining factor to the development of cancer and pathogen susceptibility of older individuals [ 32 ].…”

Section: T Cell Factormentioning

confidence: 99%

The Potential of T Cell Factor 1 in Sustaining CD8+ T Lymphocyte-Directed Anti-Tumor Immunity

Jung

Baek

2021

Cancers

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T cell factor 1 (TCF1) is a transcription factor that has been highlighted to play a critical role in the promotion of T cell proliferation and maintenance of cell stemness in the embryonic and CD8+ T cell populations. The regulatory nature of TCF1 in CD8+ T cells is of great significance, especially within the context of T cell exhaustion, which is linked to the tumor and viral escape in pathological contexts. Indeed, inhibitory signals, such as programmed cell death 1 (PD-1) and cytotoxic-T-lymphocyte-associated protein 4 (CTLA-4), expressed on exhausted T lymphocytes (TEX), have become major therapeutic targets in immune checkpoint blockade (ICB) therapy. The significance of TCF1 in the sustenance of CTL-mediated immunity against pathogens and tumors, as well as its recently observed necessity for an effective anti-tumor immune response in ICB therapy, presents TCF1 as a potentially significant biomarker and/or therapeutic target for overcoming CD8+ T cell exhaustion and resistance to ICB therapy. In this review, we aim to outline the recent findings on the role of TCF1 in T cell development and discuss its implications in anti-tumor immunity.

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“…Given the broad role of TCF1 in T cell biology, its reduced expression with age is likely to have consequences independent of its effect on miR-181a expression. In searching for TCF1 targets that could contribute to the effect on T cell activation 42 , TCF7 decreased PIM1 transcription, while inhibition of GSK3ß decreased its expression. Moreover, PIM1 expression is increased with age, consistent with reduced TCF1 expression 43 .…”

Section: Discussionmentioning

confidence: 99%

“…miR-181a to affect T cell signaling, however, our rescue experiments proofed that miR-181 was one major pathway. Independent of TCR signaling and TCR threshold calibration, the reduced expression of TCF1 is likely to have effects on T cell differentiation and function, in part mediated through miR-181a, in part through other molecules 42,44 . Kared and colleagues found loss of TCF1 with age especially in T stem cell memory cells 45 , and activation of WNT/TCF1 signaling by inhibiting GSK3ß was found to maintain pluripotency in human and mouse embryonic stem cells 46 .…”

Section: Discussionmentioning

confidence: 99%

The GSK3β-β-catenin-TCF1 pathway improves naive T cell activation in old adults by upregulating miR-181a

Gould

Zhang

et al. 2021

npj Aging Mech Dis

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MicroRNAs play an important role in the regulation of T cell development, activation, and differentiation. One of the most abundant microRNAs in lymphocytes is miR-181a, which controls T cell receptor (TCR) activation thresholds in thymic selection as well as in peripheral T cell responses. We previously found that miR-181a levels decline in T cells in the elderly. In this study, we identified TCF1 as a transcriptional regulator of pri-miR-181a. A decline in TCF1 levels in old individuals accounted for the reduced miR-181a expression impairing TCR signaling. Inhibition of GSK3ß restored expression of miR-181a by inducing TCF1 in T cells from old adults. GSK3ß inhibition enhanced TCR signaling to increase downstream expression of activation markers and production of IL-2. The effect involved the upregulation of miR-181a and the inhibition of DUSP6 expression. Thus, inhibition of GSK3ß can restore responses of old T cells by inducing miR-181a expression through TCF1.

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The Transcription Factor TCF1 in T Cell Differentiation and Aging

Cited by 59 publications

References 124 publications

Immunosuppression Considerations for Older Kidney Transplant Recipients

Immunosuppression Considerations for Older Kidney Transplant Recipients

The Potential of T Cell Factor 1 in Sustaining CD8+ T Lymphocyte-Directed Anti-Tumor Immunity

The GSK3β-β-catenin-TCF1 pathway improves naive T cell activation in old adults by upregulating miR-181a

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