Fatty Acid and Carnitine Metabolism Are Dysregulated in Systemic Sclerosis Patients

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 t...

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Bibliographic Details
Published in:	Frontiers in immunology Vol. 11; p. 822
Main Authors:	Ottria, A, Hoekstra, A T, Zimmermann, M, van der Kroef, M, Vazirpanah, N, Cossu, M, Chouri, E, Rossato, M, Beretta, L, Tieland, R G, Wichers, C G K, Stigter, E, Gulersonmez, C, Bonte-Mineur, F, Berkers, C R, Radstake, T R D J, Marut, W
Format:	Journal Article
Language:	English
Published:	Switzerland Frontiers Media S.A 22-05-2020
Subjects:	Adult Aged Carnitine - blood carnitines Cohort Studies Cytokines - metabolism dendritic cells Dendritic Cells - metabolism Etoposide - pharmacology fatty acid oxidation Fatty Acids - blood Female Fibrosis - genetics Gene Expression - drug effects Humans Immunology Inflammation - genetics Inflammation - immunology Inflammation - metabolism Male Metabolome metabolomics Metabolomics - methods Middle Aged Organic Cation Transport Proteins - antagonists & inhibitors Oxidation-Reduction - drug effects Scleroderma, Systemic - blood Scleroderma, Systemic - immunology Signal Transduction - drug effects systemic sclerosis carnitines dendritic cells systemic sclerosis fatty acid oxidation metabolomics
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Summary:	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.
Bibliography:	Reviewed by: Carlo Chizzolini, Université de Genève, Switzerland; Janine Adele Lamb, University of Manchester, United Kingdom Edited by: Dimitrios Petrou Bogdanos, University of Thessaly, Greece This article was submitted to Autoimmune and Autoinflammatory Disorders, a section of the journal Frontiers in Immunology
ISSN:	1664-3224 1664-3224
DOI:	10.3389/fimmu.2020.00822