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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139
Rogakou, E. P., Pilch, D. R., Orr, A. H., Ivanova, V. S., & Bonner, W. M. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.10.5858 · Cited by 5,438
Extension of Life-Span by Introduction of Telomerase into Normal Human Cells
Bodnar, A. G., Ouellette, M., Frolkis, M., Holt, S. E., Chiu, C.-P., Morin, G. B., Harley, C. B., Shay, J. W., Lichtsteiner, S., & Wright, W. E. (1998) · Science · doi:10.1126/science.279.5349.349 · Cited by 4,975
Telomere measurement by quantitative PCR
Cawthon, R. (2002) · Nucleic Acids Research · doi:10.1093/nar/30.10.e47 · Cited by 3,550
Shelterin: the protein complex that shapes and safeguards human telomeres
de Lange, T. (2005) · Genes & Development · doi:10.1101/gad.1346005 · Cited by 3,056
Switching and Signaling at the Telomere
Blackburn, E. H. (2001) · Cell · doi:10.1016/s0092-8674(01)00492-5 · Cited by 2,139
Doran, M. F., Crowson, C. S., Pond, G. R., O’Fallon, W. M., & Gabriel, S. E. (2002) · Arthritis & Rheumatism · doi:10.1002/art.10524 · Cited by 1,213
Aubert, G., & Lansdorp, P. M. (2008) · Physiological Reviews · doi:10.1152/physrev.00026.2007 · Cited by 1,188
The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita
Vulliamy, T., Marrone, A., Goldman, F., Dearlove, A., Bessler, M., Mason, P. J., & Dokal, I. (2001) · Nature · doi:10.1038/35096585 · Cited by 960
McEachern, M. J., Krauskopf, A., & Blackburn, E. H. (2000) · Annual Review of Genetics · doi:10.1146/annurev.genet.34.1.331 · Cited by 716
Quah, B., Warren, H. S., & Parish, C. R. (2007) · Nature Protocols · doi:10.1038/nprot.2007.296 · Cited by 636
Cited by
Sorted by citations
Understanding immunosenescence to improve responses to vaccines
Goronzy, J. J., & Weyand, C. M. (2013) · Nature Immunology · doi:10.1038/ni.2588 · Cited by 827
Self-citationAging of the Immune System. Mechanisms and Therapeutic Targets
Weyand, C. M., & Goronzy, J. J. (2016) · Annals of the American Thoracic Society · doi:10.1513/annalsats.201602-095aw · Cited by 586
Self-citationInflammaging and Oxidative Stress in Human Diseases: From Molecular Mechanisms to Novel Treatments
Zuo, L., Prather, E. R., Stetskiv, M., Garrison, D. E., Meade, J. R., Peace, T. I., & Zhou, T. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20184472 · Cited by 560
Successful and Maladaptive T Cell Aging
Goronzy, J. J., & Weyand, C. M. (2017) · Immunity · doi:10.1016/j.immuni.2017.03.010 · Cited by 362
Self-citationAgeing and the telomere connection: An intimate relationship with inflammation
Zhang, J., Rane, G., Dai, X., Shanmugam, M. K., Arfuso, F., Samy, R. P., Lai, M. K. P., Kappei, D., Kumar, A. P., & Sethi, G. (2015) · Ageing Research Reviews · doi:10.1016/j.arr.2015.11.006 · Cited by 396
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
