Fatty Acid and Carnitine Metabolism Are Dysregulated in Systemic Sclerosis Patients

A. Ottria, A. T. Hoekstra, M. Zimmermann, M. van der Kroef, N. Vazirpanah, M. Cossu, E. Chouri, M. Rossato, L. Beretta, R. G. Tieland, C. G.K. Wichers, E. Stigter, C. Gulersonmez, F. Bonte-Mineur, C. R. Berkers, T. R.D.J. Radstake, W. Marut

Research output: Contribution to journalArticlepeer-review

Abstract

Systemic sclerosis (SSc) is a rare chronic disease of unknown pathogenesis characterized by fibrosis of the skin and internal organs, vascular alteration, and dysregulation of the immune system. In order to better understand the immune system and its perturbations leading to diseases, the study of the mechanisms regulating cellular metabolism has gained a widespread interest. Here, we have assessed the metabolic status of plasma and dendritic cells (DCs) in patients with SSc. We identified a dysregulated metabolomic signature in carnitine in circulation (plasma) and intracellularly in DCs of SSc patients. In addition, we confirmed carnitine alteration in the circulation of SSc patients in three independent plasma measurements from two different cohorts and identified dysregulation of fatty acids. We hypothesized that fatty acid and carnitine alterations contribute to potentiation of inflammation in SSc. Incubation of healthy and SSc dendritic cells with etoposide, a carnitine transporter inhibitor, inhibited the production of pro-inflammatory cytokines such as IL-6 through inhibition of fatty acid oxidation. These findings shed light on the altered metabolic status of the immune system in SSc patients and opens up for potential novel avenues to reduce inflammation.

Original languageEnglish
Article number822
JournalFrontiers in Immunology
Volume11
DOIs
Publication statusPublished - Jan 1 2020

Keywords

  • carnitines
  • dendritic cells
  • fatty acid oxidation
  • metabolomics
  • systemic sclerosis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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