The immunology of rheumatoid arthritis

Cornelia M. Weyand, Jörg J. Goronzy

Research output: Contribution to journalReview articlepeer-review

4 Scopus citations

Abstract

The immunopathogenesis of rheumatoid arthritis (RA) spans decades, beginning with the production of autoantibodies against post-translationally modified proteins (checkpoint 1). After years of asymptomatic autoimmunity and progressive immune system remodeling, tissue tolerance erodes and joint inflammation ensues as tissue-invasive effector T cells emerge and protective joint-resident macrophages fail (checkpoint 2). The transition of synovial stromal cells into autoaggressive effector cells converts synovitis from acute to chronic destructive (checkpoint 3). The loss of T cell tolerance derives from defective DNA repair, causing abnormal cell cycle dynamics, telomere fragility and instability of mitochondrial DNA. Mitochondrial and lysosomal anomalies culminate in the generation of short-lived tissue-invasive effector T cells. This differentiation defect builds on a metabolic platform that shunts glucose away from energy generation toward the cell building and motility programs. The next frontier in RA is the development of curative interventions, for example, reprogramming T cell defects during the period of asymptomatic autoimmunity.

Original languageEnglish (US)
Pages (from-to)10-18
Number of pages9
JournalNature immunology
Volume22
Issue number1
DOIs
StatePublished - Jan 2021

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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