The telomere/telomerase system in autoimmune and systemic immune-mediated diseases.
Telomeres are specialized nucleoproteic structures that cap and protect the ends of chromosomes. They can be elongated by the telomerase enzyme, but in telomerase negative cells, telomeres shorten after each cellular division because of the end replicating problem. This phenomenon leads ultimately to cellular senescence, conferring to the telomeres a role of biological clock. Oxidative stress, inflammation and increased cell renewal are supplementary environmental factors that accelerate age-related telomere shortening. Similar to other types of DNA damage, very short/dysfunctional telomeres activate a DNA response pathway leading to different outcomes: DNA repair, cell senescence or apoptosis. During the last 10 years, studies on the telomere/telomerase system in autoimmune and/or systemic immune-mediated diseases have revealed its involvement in relevant physiopathological processes. Here, we present a literature review of telomere and telomerase homeostasis in systemic inflammatory diseases including systemic lupus erythematosus, rheumatoid arthritis and granulomatous diseases. The available data indicate that both telomerase activity and telomere length are modified in various systemic immune-mediated diseases and appear to be connected with premature immunosenescence. Studies on the telomere/telomerase system open new research avenues for the basic understanding and for therapeutic approaches of these pathologies.
Georgin-Lavialle
Sophie
S
Department of Adult Haematology, Necker Enfants-Malades Hospital, Mastocytosis Reference Center, Paris Descartes University, Paris, France.
Aouba
Achille
A
Mouthon
Luc
L
Londono-Vallejo
J Arturo
JA
Lepelletier
Yves
Y
Gabet
Anne-Sophie
AS
Hermine
Olivier
O
D019588:Aging, Premature / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D001327:Autoimmune Diseases / Q000235:genetics*; D016922:Cellular Senescence / Q000235:genetics / Q000276:immunology*; D004249:DNA Damage; D004789:Enzyme Activation; D006801:Humans; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000235:genetics / Q000276:immunology*
D019098:Telomerase