By this measure, T cells, or white blood cells, from patients with the autoimmune disease rheumatoid arthritis are worn out and prematurely aged, scientists at Emory University School of Medicine have discovered.
Compared with cells from healthy people, T cells from patients with rheumatoid arthritis have trouble turning on the enzyme that replenishes telomeres, they found. Reversing this defect could possibly help people prone to the disease maintain a balanced immune system.
The results are published online this week in Proceedings of the National Academy of Sciences.
In rheumatoid arthritis, T cells are chronically over-stimulated, invading the tissue of the joints and causing painful inflammation. This derangement can be seen as a result of the loss of the immune system's ability to discriminate friend from foe, says senior author Cornelia Weyand, MD, PhD, co-director of the Kathleen B. and Mason I. Lowance Center for Human Immunology at Emory University.
In childhood, new T cells are continually produced in the thymus, she says. But after about age 40, the thymus "involutes" – or shrinks and ceases to function. After that, the immune system has to make do with the pool of T cells it already has.
"What we see in rheumatoid arthritis is an aged and more restricted T cell repertoire," she says. "This biases the immune system toward autoimmunity."
Weyand, postdoctoral fellow Hiroshi Fujii, MD, PhD, and their colleagues were interested in mechanisms of T cells' premature aging, because scientists had previously observed that in rheumatoid arthritis, T cells tend to shift the molecules on their surface and function differently.
They found the answer in telomerase, the enzyme that renews telomeres and is necessary to prevent loss of genetic information after repeated cell division.
Telomerase adds short repeated DNA sequences to the ends of chromosomes to protect them. The enzyme is active in embryonic development but is usually switched off in adult cells. Many cancer cells reactivate it to enable runaway growth.
T cells are some of the very few cells in adults that can turn on telomerase when stimulated, probably because they have to divide many times and stay alive for decades.
Weyand and Fujii found that T cells from patients with rheumatoid arthritis make 40 percent less telomerase enzyme when stimulated. The cells came from 69 patients, 92 percent female, with an average age of 50, and were compared with cells from healthy people with similar demographics.
Shutting off a gene encoding part of the enzyme made normal T cells vulnerable to programmed cell death, and transferring telomerase into patients' T cells rescued them from dying.
The finding suggests that restoring defective telomerase to T cells could possibly help "reset" the immune system in rheumatoid arthritis, Weyand says.
Pharmaceutical industry researchers have been looking for drugs that could elevate or depress telomerase activity, with the goal of either prolonging life or treating cancer. However, turning on telomerase indiscriminately could lead to cancer, so any treatment would have to be targeted to the right cells, she says.
Holly Korschun | EurekAlert!
Further reports about: > DNA sequence > Immune cell activation > T cells > autoimmune disease rheumatoid arthritis > balanced immune system > blood cell > cancer prevention > cell death > immune system > painful inflammation > prematurely aged chromosomes > replenishes telomeres > rheumatoid arthritis > similar demographics > telomerase enzyme > white blood cell
Not of Divided Mind
19.01.2017 | Hertie-Institut für klinische Hirnforschung (HIH)
CRISPR meets single-cell sequencing in new screening method
19.01.2017 | CeMM Forschungszentrum für Molekulare Medizin der Österreichischen Akademie der Wissenschaften
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
19.01.2017 | Earth Sciences
19.01.2017 | Life Sciences
19.01.2017 | Physics and Astronomy