Frontiers in Immunology (May 2020)
Fatty Acid and Carnitine Metabolism Are Dysregulated in Systemic Sclerosis Patients
- A. Ottria,
- A. Ottria,
- A. T. Hoekstra,
- M. Zimmermann,
- M. Zimmermann,
- M. van der Kroef,
- M. van der Kroef,
- N. Vazirpanah,
- N. Vazirpanah,
- M. Cossu,
- M. Cossu,
- E. Chouri,
- E. Chouri,
- M. Rossato,
- M. Rossato,
- L. Beretta,
- R. G. Tieland,
- R. G. Tieland,
- C. G. K. Wichers,
- C. G. K. Wichers,
- E. Stigter,
- C. Gulersonmez,
- F. Bonte-Mineur,
- C. R. Berkers,
- C. R. Berkers,
- T. R. D. J. Radstake,
- T. R. D. J. Radstake,
- W. Marut,
- W. Marut
Affiliations
- A. Ottria
- Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
- A. Ottria
- Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
- A. T. Hoekstra
- Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, Netherlands
- M. Zimmermann
- Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
- M. Zimmermann
- Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
- M. van der Kroef
- Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
- M. van der Kroef
- Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
- N. Vazirpanah
- Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
- N. Vazirpanah
- Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
- M. Cossu
- Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
- M. Cossu
- Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
- E. Chouri
- Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
- E. Chouri
- Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
- M. Rossato
- Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
- M. Rossato
- Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
- L. Beretta
- Referral Center for Systemic Autoimmune Diseases, University of Milan and Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy
- R. G. Tieland
- Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
- R. G. Tieland
- Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
- C. G. K. Wichers
- Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
- C. G. K. Wichers
- Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
- E. Stigter
- Department of Molecular Cancer Research, Center Molecular Medicine, Oncode Institute, University Medical Center Utrecht, Utrecht, Netherlands
- C. Gulersonmez
- Department of Molecular Cancer Research, Center Molecular Medicine, Oncode Institute, University Medical Center Utrecht, Utrecht, Netherlands
- F. Bonte-Mineur
- Department of Rheumatology and Clinical Immunology, Maasstad Hospital, Rotterdam, Netherlands
- C. R. Berkers
- Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, Netherlands
- C. R. Berkers
- Department of Biochemistry and Cell Biology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands
- T. R. D. J. Radstake
- Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
- T. R. D. J. Radstake
- Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
- W. Marut
- Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
- W. Marut
- Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
- DOI
- https://doi.org/10.3389/fimmu.2020.00822
- Journal volume & issue
-
Vol. 11
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.
Keywords
