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Potential role of mesenchymal stem cells in T cell aging

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Abstract

Immunosenescence occurs with progressive age. T cell aging is manifested by immunodeficiency and inflammation. The main mechanisms are thymic involution, mitochondrial dysfunction, genetic and epigenetic alterations, loss of protein stability, reduction of T cell receptor (TCR) repertoire, naïve-memory T cell ratio imbalance, T cell senescence, and lack of effector plasticity. Mesenchymal stem cells (MSCs) are thought to hold great potential as anti-aging therapy. However, the role of MCSs in T cell aging remains elusive. This review makes a tentative summary of the potential role of MSCs in the protection against T cell aging. It might provide a new idea to intervene in the aging of the immune system.

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All data generated or analyzed during this study are included in this published article.

Abbreviations

TCR:

T cell receptor

MSCs:

1Mesenchymal stem cells

EPO:

Erythropoietin

TNF-α:

Tumor necrosis factor α

IFN-γ:

Interferon γ

TLR4:

Toll-like receptor 4

LPS:

Lipopolysaccharides

TLR3:

Toll-like receptor 3

IL-6:

Interleukin-6

IL-8:

Interleukin-8

TGF-β:

Transforming growth factor β

IL-4:

Interleukin-4

IL-1RA:

Interleukin-1 receptor antagonist

IDO:

Indoleamine 2,3-dioxygenase

PGE2:

Prostaglandin e2

HLA-G5:

Human leukocyte antigen g5

Th2:

T helper 2 cell

Th17:

T helper 17 cell

Th1:

T helper 1 cell

CXCR3:

Chemokine receptor chemokine (C-X-C motif) receptor 3

CTEC:

Cortical thymic epithelial cells

DN:

CD4 and CD8 double negative T cells

DP:

CD4 and CD8 double positive T cells

SP:

CD4 or CD8 single positive T cells

MHC:

Major histocompatibility complexes

EGF:

Epidermal growth factor

IGF:

Insulin-like growth factor

TEC:

Thymic epithelial cell

S1P:

Sphingosine-1-phosphate

nTMSC:

MSCs derived from human neonatal thymus

MHC-II:

Major histocompatibility complex class II

MHC-I:

Major histocompatibility complex class I

T-MSCs:

Tonsillar mesenchymal stem cells

BMT:

Bone marrow transplantation

FLT3L:

Fms-related tyrosine kinase 3 ligand

FGF7:

Fibroblast growth factor 7

PBM:

Photobiomodulation

ATP:

Adenosine triphosphate

ROS:

Reactive oxygen species

HGF:

Hepatocyte growth factor

HGF-hATMSCs:

HGF-overexpressing adipose tissue-derived mesenchymal stem cells

UC-MSCs:

Umbilical cord mesenchymal stem cells

KGF:

Keratinocyte growth factor

NAD:

Nicotinamide adenine dinucleotide

NADH:

Nicotinamide adenine dinucleotide (reduced state)

TNT:

Tunneling nanotubes

PBMC:

Peripheral blood mononuclear cells

FOXP3:

Forkhead box protein P3

IL2RA:

Interleukin-2 receptor subunit alpha

CTLA4:

Cytotoxic t lymphocyte-associated antigen-4

iTreg:

Induced regulatory T cells

MT:

Mitochondrial transfer

CDKN1A:

Cyclin-dependent kinase inhibitor 1A

MRE11A:

Meiotic recombination 11 homolog A

CDKN2A:

Cyclin-dependent kinase inhibitor 2A

PD-1:

Programmed cell death protein 1

ROR-γ:

Related-orphan receptors γ

SIRT1:

Sirtuin1

VEGF:

Vascular endothelial growth factor

PCNA:

Proliferating cell nuclear antigen

AGRP:

Agouti gene-related protein

STAT3:

Signal transducer and activator of transcription 3

ICAM-1:

Intercellular cell adhesion molecule-1

Tfh:

Follicular helper T cells

OA:

Osteoarthritis

Nrf2:

Nuclear erythroid 2-related factor 2

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Funding

This work was supported by the National Natural Science Foundation of China (No. 81972643, No. 82172962), the Sichuan Science and Technology Project (2021YJ0201), the Luxian People’s Government and Southwest Medical University Scientific and Technological Achievements Transfer and Transformation Strategic Cooperation Project (2019LXXNYKD-07), and the Science and Technology Program of Luzhou, China (No. 2017LZXNYD-Z04, No. 21CGZHPT0001).

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Authors and Affiliations

  1. Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, No. 1, Section 1, Xianglin Road, Longmatan District, Luzhou, 646000, Sichuan, China

    Xianmei Zhong, Jie Chen, Bo Wen, Xu Wu, Mingxing Li, Fukuan Du, Yu Chen, Shuai Deng, Yueshui Zhao, Jing Shen & Zhangang Xiao

  2. Department of Pharmacy, People’s Hospital of Nanbu County, Nanchong, 637300, China

    Xianmei Zhong

  3. South Sichuan Institute of Translational Medicine, Luzhou, 646000, Sichuan, China

    Xu Wu, Mingxing Li, Fukuan Du, Yu Chen, Shuai Deng, Yueshui Zhao, Jing Shen & Zhangang Xiao

  4. Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou, 646000, Sichuan, China

    Xu Wu, Mingxing Li, Fukuan Du, Yu Chen, Shuai Deng, Yueshui Zhao, Jing Shen & Zhangang Xiao

Authors
  1. Xianmei Zhong
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  2. Jie Chen
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  3. Bo Wen
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  4. Xu Wu
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  5. Mingxing Li
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  6. Fukuan Du
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  7. Yu Chen
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  8. Shuai Deng
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  9. Yueshui Zhao
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  10. Jing Shen
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  11. Zhangang Xiao
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Contributions

Yueshui Zhao and Jing Shen had the idea for the article. Jie Chen and Bo Wen performed the literature search and data analysis. Xianmei Zhong, Xu Wu, Mingxing Li, Fukuan Du, Yu Chen, and Shuai Deng drafted and critically revised the work. Zhangang Xiao acquired the funding for the work. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Zhangang Xiao.

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Zhong, X., Chen, J., Wen, B. et al. Potential role of mesenchymal stem cells in T cell aging. J Mol Med 101, 1365–1378 (2023). https://doi.org/10.1007/s00109-023-02371-y

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