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Updated: Jun 25, 2026
07:37
An Adoptive Transfer Model of Rheumatoid Arthritis in Mice
Published on: June 6, 2025
Telomerase insufficiency in rheumatoid arthritis
Hiroshi Fujii1, Lan Shao, Inés Colmegna
1Department of Medicine, Lowance Center for Human Immunology and Rheumatology, Emory University School of Medicine, 101 Woodruff Circle, Atlanta, GA 30322, USA.
Summary
Rheumatoid arthritis (RA) involves T cells with shortened telomeres and defective telomerase activity, leading to increased apoptosis. Restoring telomerase function may offer a new therapeutic strategy for RA immune dysfunction.
Area of Science:
- Immunology
- Molecular Biology
- Gerontology
Background:
- Rheumatoid arthritis (RA) is characterized by chronic T lymphocyte stimulation causing joint inflammation.
- T cells in RA exhibit premature aging with accelerated telomere shortening, indicating excessive proliferation or impaired telomere maintenance.
Purpose of the Study:
- To investigate the role of telomerase activity and human telomerase reverse transcriptase (hTERT) in T cell dysfunction in RA.
- To explore telomerase insufficiency as a potential therapeutic target for immune abnormalities in RA.
Main Methods:
- Analysis of telomerase activity and hTERT expression in naïve and memory CD4 T cells from RA patients.
- Knockdown and overexpression of hTERT in primary human T cells to assess apoptosis and proliferation.
- Assessment of T cell activation, cell cycle progression, and clonal expansion.
Main Results:
- Naïve CD4 T cells in RA show defective telomerase upregulation upon stimulation due to insufficient hTERT induction, despite intact T cell activation.
- hTERT knockdown increases apoptosis and limits clonal expansion in T cells, while hTERT overexpression confers apoptotic resistance and restores proliferation.
- Telomerase insufficiency is present in untreated RA patients, independent of disease activity, and affects only naïve T cells and CD34 hematopoietic stem cells.
Conclusions:
- Defective telomerase activity in RA naïve T cells leads to excessive apoptosis and impaired immune homeostasis, potentially driving repertoire remodeling.
- Restoring telomerase activity presents a promising therapeutic avenue for correcting immune abnormalities in rheumatoid arthritis.
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