Abstract
Introduction
The incidence of rheumatoid arthritis (RA) and its complications are expected to increase with age. Remarkably, RA patients were identified features of accelerated aging, particularly in immunosenescence. As is known, T cells in RA patients readily differentiate into pro-inflammatory phenotypes that maintain chronic and persistent inflammatory changes in joints and many other organ systems. Recent evidence suggests that T cells are most sensitive to aging, and aged CD4+ T cells contribute to inflammaging, which plays a crucial role in accelerating the disease process. In recent years, the molecular mechanisms of T cell immunosenescence were beginning to be understood. Immune aging in RA T cells is associated with thymus insufficiency, metabolic abnormalities, shortened telomere length, and chronic energy stress. Therefore, we summarized the role and mechanism of T cell immunosenescence in RA.
Methods
A computer-based online search was performed using the PubMed database for published articles concerning T cells aging and rheumatoid arthritis.
Results
In this review, we assess the roles of CD4+ T cells in the center of inflammaging especially in RA and emphasize arthritogenic effector functions of senescent T cell; also we discuss the possible molecular mechanisms of senescent T cells and therapeutic targets to intervene T cells immunosenescence for improvement of RA.
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Abbreviations
- SASP:
-
Senescence-associated secretory phenotype
- TCR:
-
T cell receptor
- TEMRA:
-
Terminally differentiated effector memory T cell
- IGF-1:
-
Insulin-like growth factor-1
- FOXO:
-
Forkhead box O
- mTOR:
-
Mechanistic target of rapamycin
- MMPs:
-
Matrix metalloproteinases
- RANKL:
-
Receptor activator of nuclear factor-κB ligand
- Wnt:
-
Wingless/integrated
- LRP5/6:
-
LDL-receptor-related protein 5/6
- DDK-1:
-
Dickkopf-related protein 1
- ATM:
-
Ataxia telangiectasia-mutated
- DNA-PKcs:
-
DNA dependent protein kinase catalytic subunit
- PFKFB3:
-
Phosphofructokinase/fructose biphosphatase3
- G6PD:
-
Glucose-6-phosphate dehydrogenease
- DDR:
-
DNA damage response
- TCA:
-
Tricarboxylic acid cycle
- AMPK:
-
Adenosine 5’-monophosphate-activated protein kinase
- mTORC1:
-
Mechanistic target of rapamycin complex1
- PTEN:
-
Phosphatase and tensin homolog deleted on chromosome ten
- SIRT1:
-
NAD + -dependent deacetylase sirtuin-1
- Nrf2:
-
Nuclear factor erythroid2-related factor 2
- NHEJ:
-
Non-homologous end joining
- NMT1:
-
N-myristoyltransferase 1
- Drp1:
-
Dynamin-related protein 1
- PGC1α:
-
Peroxisome proliferator-activated receptor-γ coactivator-1α
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Acknowledgements
The authors wish to acknowledge Anhui engineering technology research center of biochemical pharmaceutical for the support of experimental equipment.
Funding
This work was supported by grants from the National Natural Science Foundation of China (81703529), 512 Talent Training Program of Bengbu Medical College (by51202203), the Major research project of Education Department of Anhui Province (KJ2021ZD0086), Scientific and Technological Collaboration Project of Bengbu and Bengbu Medical College (BYLK201819), The Innovation and Entrepreneurship Project Plan of National Undergraduate Support Project of China (202010367037, 202110367020).
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YG designed and conducted the literature review and drafted the manuscript. WC, YZ, YL, and JC conducted the literature review. FW designed and conceptualized the manuscript. All authors reviewed and approved the manuscript.
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Gao, Y., Cai, W., Zhou, Y. et al. Immunosenescence of T cells: a key player in rheumatoid arthritis. Inflamm. Res. 71, 1449–1462 (2022). https://doi.org/10.1007/s00011-022-01649-0
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DOI: https://doi.org/10.1007/s00011-022-01649-0