T-cell Immunoglobulin and ITIM Domain Contributes to CD8 + T-cell Immunosenescence

Yangzi Song, Beibei Wang, Rui Song, Yu Hao, Di Wang, Yuxin Li, Yu Jiang, Ling Xu, Yaluan Ma, Hong Zheng, Yaxian Kong, Hui Zeng

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Aging is associated with immune dysfunction, especially T-cell defects, which result in increased susceptibility to various diseases. Previous studies showed that T cells from aged mice express multiple inhibitory receptors, providing evidence of the relationship between T-cell exhaustion and T-cell senescence. In this study, we showed that T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT), a novel co-inhibitory receptor, was upregulated in CD8 + T cells of elderly adults. Aged TIGIT + CD8 + T cells expressed high levels of other inhibitory receptors including PD-1 and exhibited features of exhaustion such as downregulation of the key costimulatory receptor CD28, representative intrinsic transcriptional regulation, low production of cytokines, and high susceptibility to apoptosis. Importantly, their functional defects associated with aging were reversed by TIGIT knockdown. CD226 downregulation on aged TIGIT + CD8 + T cells is likely involved in TIGIT-mediated negative immune suppression. Collectively, our findings indicated that TIGIT acts as a critical immune regulator during aging, providing a strong rationale for targeting TIGIT to improve dysfunction related to immune system aging.

Original languageEnglish (US)
Article numbere12716
JournalAging cell
Volume17
Issue number2
DOIs
StatePublished - Apr 1 2018

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Tyrosine
Immunoglobulins
T-Lymphocytes
Programmed Cell Death 1 Receptor
Down-Regulation
Immunosenescence
Cell Aging
Immune System
Apoptosis
Cytokines

All Science Journal Classification (ASJC) codes

  • Aging
  • Cell Biology

Cite this

Song, Y., Wang, B., Song, R., Hao, Y., Wang, D., Li, Y., ... Zeng, H. (2018). T-cell Immunoglobulin and ITIM Domain Contributes to CD8 + T-cell Immunosenescence Aging cell, 17(2), [e12716]. https://doi.org/10.1111/acel.12716
Song, Yangzi ; Wang, Beibei ; Song, Rui ; Hao, Yu ; Wang, Di ; Li, Yuxin ; Jiang, Yu ; Xu, Ling ; Ma, Yaluan ; Zheng, Hong ; Kong, Yaxian ; Zeng, Hui. / T-cell Immunoglobulin and ITIM Domain Contributes to CD8 + T-cell Immunosenescence In: Aging cell. 2018 ; Vol. 17, No. 2.
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abstract = "Aging is associated with immune dysfunction, especially T-cell defects, which result in increased susceptibility to various diseases. Previous studies showed that T cells from aged mice express multiple inhibitory receptors, providing evidence of the relationship between T-cell exhaustion and T-cell senescence. In this study, we showed that T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT), a novel co-inhibitory receptor, was upregulated in CD8 + T cells of elderly adults. Aged TIGIT + CD8 + T cells expressed high levels of other inhibitory receptors including PD-1 and exhibited features of exhaustion such as downregulation of the key costimulatory receptor CD28, representative intrinsic transcriptional regulation, low production of cytokines, and high susceptibility to apoptosis. Importantly, their functional defects associated with aging were reversed by TIGIT knockdown. CD226 downregulation on aged TIGIT + CD8 + T cells is likely involved in TIGIT-mediated negative immune suppression. Collectively, our findings indicated that TIGIT acts as a critical immune regulator during aging, providing a strong rationale for targeting TIGIT to improve dysfunction related to immune system aging.",
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Song, Y, Wang, B, Song, R, Hao, Y, Wang, D, Li, Y, Jiang, Y, Xu, L, Ma, Y, Zheng, H, Kong, Y & Zeng, H 2018, ' T-cell Immunoglobulin and ITIM Domain Contributes to CD8 + T-cell Immunosenescence ', Aging cell, vol. 17, no. 2, e12716. https://doi.org/10.1111/acel.12716

T-cell Immunoglobulin and ITIM Domain Contributes to CD8 + T-cell Immunosenescence . / Song, Yangzi; Wang, Beibei; Song, Rui; Hao, Yu; Wang, Di; Li, Yuxin; Jiang, Yu; Xu, Ling; Ma, Yaluan; Zheng, Hong; Kong, Yaxian; Zeng, Hui.

In: Aging cell, Vol. 17, No. 2, e12716, 01.04.2018.

Research output: Contribution to journalArticle

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T1 - T-cell Immunoglobulin and ITIM Domain Contributes to CD8 + T-cell Immunosenescence

AU - Song, Yangzi

AU - Wang, Beibei

AU - Song, Rui

AU - Hao, Yu

AU - Wang, Di

AU - Li, Yuxin

AU - Jiang, Yu

AU - Xu, Ling

AU - Ma, Yaluan

AU - Zheng, Hong

AU - Kong, Yaxian

AU - Zeng, Hui

PY - 2018/4/1

Y1 - 2018/4/1

N2 - Aging is associated with immune dysfunction, especially T-cell defects, which result in increased susceptibility to various diseases. Previous studies showed that T cells from aged mice express multiple inhibitory receptors, providing evidence of the relationship between T-cell exhaustion and T-cell senescence. In this study, we showed that T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT), a novel co-inhibitory receptor, was upregulated in CD8 + T cells of elderly adults. Aged TIGIT + CD8 + T cells expressed high levels of other inhibitory receptors including PD-1 and exhibited features of exhaustion such as downregulation of the key costimulatory receptor CD28, representative intrinsic transcriptional regulation, low production of cytokines, and high susceptibility to apoptosis. Importantly, their functional defects associated with aging were reversed by TIGIT knockdown. CD226 downregulation on aged TIGIT + CD8 + T cells is likely involved in TIGIT-mediated negative immune suppression. Collectively, our findings indicated that TIGIT acts as a critical immune regulator during aging, providing a strong rationale for targeting TIGIT to improve dysfunction related to immune system aging.

AB - Aging is associated with immune dysfunction, especially T-cell defects, which result in increased susceptibility to various diseases. Previous studies showed that T cells from aged mice express multiple inhibitory receptors, providing evidence of the relationship between T-cell exhaustion and T-cell senescence. In this study, we showed that T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT), a novel co-inhibitory receptor, was upregulated in CD8 + T cells of elderly adults. Aged TIGIT + CD8 + T cells expressed high levels of other inhibitory receptors including PD-1 and exhibited features of exhaustion such as downregulation of the key costimulatory receptor CD28, representative intrinsic transcriptional regulation, low production of cytokines, and high susceptibility to apoptosis. Importantly, their functional defects associated with aging were reversed by TIGIT knockdown. CD226 downregulation on aged TIGIT + CD8 + T cells is likely involved in TIGIT-mediated negative immune suppression. Collectively, our findings indicated that TIGIT acts as a critical immune regulator during aging, providing a strong rationale for targeting TIGIT to improve dysfunction related to immune system aging.

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