Rejuvenating the immune system in rheumatoid arthritis

Cornelia M. Weyand, Hiroshi Fujii, Lan Shao, Jörg J. Goronzy

Research output: Contribution to journalReview articlepeer-review

67 Citations (Scopus)

Abstract

In rheumatoid arthritis (RA), the aging process of the immune system is accelerated. Formerly, this phenomenon was suspected to be a consequence of chronic inflammatory activity. However, newer data strongly suggest that deficiencies in maintaining telomeres and overall DNA stability cause excessive apoptosis of RA T cells, imposing proliferative pressure and premature aging on the system. Already during the early stages of their life cycle, and long before they participate in the inflammatory process, RA T cells are lost owing to increased apoptotic susceptibility. A search for underlying mechanisms has led to the discovery of defective pathways of repairing broken DNA and elongating and protecting telomeric sequences at the chromosomal ends. Two enzymatic machineries devoted to DNA repair and maintenance have been implicated. RA T cells fail to induce sufficient amounts of the telomeric repair enzyme telomerase, leaving telomeric ends uncapped and thus susceptible to damage. Of equal importance, RA T cells produce low levels of the DNA repair enzyme ataxia telangiectasia mutated and the complex of nucleoproteins that sense and fix DNA double-strand breaks. The inability to repair damaged DNA renders naive T cells vulnerable to apoptosis, exhausts T-cell regeneration and reshapes the T cell repertoire. Therapeutic attempts to reset the immune systems of patients with RA and prevent premature immunosenescence should include restoration of DNA repair capability.

Original languageEnglish
Pages (from-to)583-588
Number of pages6
JournalNature Reviews Rheumatology
Volume5
Issue number10
DOIs
Publication statusPublished - 2009 Oct 19

ASJC Scopus subject areas

  • Rheumatology

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