The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
Rejuvenating the immune system in rheumatoid arthritis.
Abstract
In rheumatoid arthritis (RA), the aging process of the immune system is accelerated. Formerly, this phenomenon was suspected to be a consequence of chronic inflammatory activity. However, newer data strongly suggest that deficiencies in maintaining telomeres and overall DNA stability cause excessive apoptosis of RA T cells, imposing proliferative pressure and premature aging on the system. Already during the early stages of their life cycle, and long before they participate in the inflammatory process, RA T cells are lost owing to increased apoptotic susceptibility. A search for underlying mechanisms has led to the discovery of defective pathways of repairing broken DNA and elongating and protecting telomeric sequences at the chromosomal ends. Two enzymatic machineries devoted to DNA repair and maintenance have been implicated. RA T cells fail to induce sufficient amounts of the telomeric repair enzyme telomerase, leaving telomeric ends uncapped and thus susceptible to damage. Of equal importance, RA T cells produce low levels of the DNA repair enzyme ataxia telangiectasia mutated and the complex of nucleoproteins that sense and fix DNA double-strand breaks. The inability to repair damaged DNA renders naive T cells vulnerable to apoptosis, exhausts T-cell regeneration and reshapes the T cell repertoire. Therapeutic attempts to reset the immune systems of patients with RA and prevent premature immunosenescence should include restoration of DNA repair capability.
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“The process of immunosenescence is accelerated in rheumatoid arthritis.”
From T-cell aging in rheumatoid arthritis (2014) · cites this paper as [7]
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Metadata
- Authors
- Weyand, C. M., Fujii, H., Shao, L., & Goronzy, J. J.
- Affiliations
- Emory University (US)
- Tohoku University (JP)
- Corresponding author
- Weyand, Cornelia M.
- Venue
- Nature Reviews Rheumatology
- Published
- 2009-10
- Volume
- 5
- Issue
- 10
- Pages
- 583-588
- ISSN
- 1759-4790 (ISSN-L)
- 1759-4804
- OpenAlex
- W1996651004
- Cited by
- 112
- References
- 49
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 6 · 2023: 6 · 2022: 8 · 2021: 9 · 2020: 6 · 2019: 4 · 2018: 3 · 2017: 10 · 2016: 8 · 2015: 8 · 2014: 6 · 2013: 9 · 2012: 5
- FWCI
- 0.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Rheumatology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American College of Rheumatology Research and Education Foundation
- Rheumatology Research Foundation
- National Institutes of Health
- National Institute on Aging (R01AG015043, AG 15043)
- National Institute of Allergy and Infectious Diseases (AI 57266, AI 44142, U19AI057266)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR041974, AR42527, R01AR042527, AR 41974)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- rheumatoid arthritis, immunosenescence, T cell apoptosis, telomeres, telomerase, DNA repair, ATM kinase, DNA double-strand break repair, T cell exhaustion, T cell receptor repertoire
- MeSH terms
- Aging, Arthritis, Rheumatoid, DNA Damage, DNA Repair, DNA-Binding Proteins, Humans, Immune System, Rejuvenation, T-Lymphocytes, Telomere, Apoptosis, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Telomerase, Tumor Suppressor Proteins, DNA Breaks, Double-Stranded, Ataxia Telangiectasia Mutated Proteins
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