The DOI matches its Crossref record; 44 of the 45 references it cites were found in a registry or an index.
Telomerase insufficiency in rheumatoid arthritis
Open accessAbstract
In rheumatoid arthritis (RA), chronically stimulated T lymphocytes sustain tissue-destructive joint inflammation. Both naïve and memory T cells in RA are prematurely aged with accelerated loss of telomeres suggesting excessive proliferative pressure or inadequate telomeric maintenance. Upon stimulation, RA naïve CD4 T cells are defective in up-regulating telomerase activity ( P < 0.0001) due to insufficient induction of the telomerase component human telomerase reverse transcriptase (hTERT); T cell activation and cell cycle progression are intact. Telomerase insufficiency does not affect memory T cells or CD34 hematopoietic stem cells and is present in untreated patients and independent from disease activity. Knockdown of hTERT in primary human T cells increases apoptotic propensity ( P = 0.00005) and limits clonal burst ( P = 0.0001) revealing a direct involvement of telomerase in T cell fate decisions. Naïve RA CD4 T cells stimulated through the T cell receptor are highly susceptible to apoptosis, expanding to smaller clonal size. Overexpression of ectopic hTERT in naïve RA T cells conveys apoptotic resistance ( P = 0.008) and restores proliferative expansion ( P < 0.0001). Telomerase insufficiency in RA results in excessive T cell loss, undermining homeostatic control of the naive T cell compartment and setting the stage for lymphopenia-induced T cell repertoire remodeling. Restoring defective telomerase activity emerges as a therapeutic target in resetting immune abnormalities in RA.
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In the citing paper
“Early studies, utilizing measurements of telomeric length and clonal expansion of CD4+CD28− end-differentiated T cells, estimated that the immune aging process is accelerated by 2–3 decades in patients with RA as compared to age-matched controls”
From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Fujii et al., 2009
Experimental — accuracy not yet measuredIn the citing paper
“This mechanism of telomerase upregulation is defective in patients with RA, shortening the longevity of T cells [14].”
From T-cell aging in rheumatoid arthritis (2014) · cites this paper as [14]
In the citing paper
“This compensatory mechanism is defective in RA T cells [14,53].”
From T-cell aging in rheumatoid arthritis (2014) · cites this paper as [14]
In the citing paper
“It is also estimated that naïve T cells expand by 30–40 population doublings during priming alone [14].”
From T-cell aging in rheumatoid arthritis (2014) · cites this paper as [14]
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Metadata
- Authors
- Fujii, H., Shao, L., Colmegna, I., Goronzy, J. J., & Weyand, C. M.
- Affiliations
- Emory University (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2009-03-17
- Volume
- 106
- Issue
- 11
- Pages
- 4360-4365
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2657451
- OpenAlex
- W2067557887
- Cited by
- 172
- References
- 45
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 11 · 2023: 6 · 2022: 10 · 2021: 7 · 2020: 16 · 2019: 15 · 2018: 11 · 2017: 10 · 2016: 9 · 2015: 11 · 2014: 8 · 2013: 13 · 2012: 11
- FWCI
- 8.39
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (UL1TR000454)
- National Institute on Aging (R01AG015043, R01AG15043)
- National Heart, Lung, and Blood Institute (R01HL117913)
- National Eye Institute (R01EY011916)
- National Institute of Allergy and Infectious Diseases (R01AI044142, R01 AI57266, R01AI44142, R01AI108906, R56AI044142, U19AI057266)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR041974, R01 AR 41974, R01AR042527, R01AR42527)
- National Center for Advancing Translational Sciences
- 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, human telomerase reverse transcriptase, hTERT, T cell senescence, naive CD4+ T cells, memory T cells, T cell apoptosis, clonal expansion, lymphopenia, T cell receptor stimulation, hematopoietic stem cells, joint inflammation, telomere length
- MeSH terms
- Arthritis, Rheumatoid, Hematopoietic Stem Cells, Humans, Immunologic Memory, T-Lymphocytes, Down-Regulation, Case-Control Studies, Telomere, Cellular Senescence, Telomerase
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