The metabolic signature of T cells in rheumatoid arthritis

Cornelia M. Weyand, Bowen Wu, Jörg J. Goronzy

Research output: Contribution to journalReview articlepeer-review

4 Scopus citations

Abstract

Purpose of reviewRheumatoid arthritis (RA) is a prototypic autoimmune disease manifesting as chronic inflammation of the synovium and leading to acceleration of cardiovascular disease and shortening of life expectancy. The basic defect causing autoimmunity has remained elusive, but recent insights have challenged the notion that autoantigen is the core driver.Recent findingsEmerging data have added metabolic cues involved in the proper maintenance and activation of immune cells as pathogenic regulators. Specifically, studies have unveiled metabolic pathways that enforce T cell fate decisions promoting tissue inflammation; including T cell tissue invasiveness, T cell cytokine release, T cell-dependent macrophage activation and inflammatory T cell death. At the center of the metabolic abnormalities lies the mitochondria, which is consistently underperforming in RA T cells. The mitochondrial defect results at least partially from insufficient DNA repair and leads to lipid droplet accumulation, formation of invasive membrane ruffles, inflammasome activation and pyroptotic T cell death.SummaryT cells in patients with RA, even naïve T cells never having been involved in inflammatory lesions, have a unique metabolic signature and the changes in intracellular metabolites drive pathogenic T cell behavior. Recognizing the role of metabolic signals in cell fate decisions opens the possibility for immunomodulation long before the end stage synovial inflammation encountered in clinical practice.

Original languageEnglish (US)
Pages (from-to)159-167
Number of pages9
JournalCurrent opinion in rheumatology
Volume32
Issue number2
DOIs
StatePublished - Mar 1 2020

Keywords

  • glycolysis
  • inflammasome
  • macrophage
  • mitochondria
  • pyroptosis
  • rheumatoid arthritis
  • T cell

ASJC Scopus subject areas

  • Rheumatology

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