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Immunosenescence of T cells: a key player in rheumatoid arthritis

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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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Authors and Affiliations

  1. School of Pharmacy, Bengbu Medical College, 2600, Donghai Avenue, Bengbu, 233030, Anhui, China

    Yi Gao, Weiwei Cai, Yuhui Li, Jingwen Cheng & Fang Wei

  2. Anhui Engineering Technology Research Center of Biochemical Pharmaceutical, 2600 Donghai Avenue, Bengbu, 233030, Anhui, China

    Fang Wei

  3. Department of Rheumatology and Immunology, The First Affiliated Hospital to Bengbu Medical College, Bengbu, 233000, Anhui, China

    Ying Zhou

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  1. Yi Gao
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  2. Weiwei Cai
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  3. Ying Zhou
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  4. Yuhui Li
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  5. Jingwen Cheng
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  6. Fang Wei
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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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Correspondence to Fang Wei.

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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

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