Soluble alpha-enolase activates monocytes by CD14-dependent TLR4 signalling pathway and exhibits a dual function

• Published in: Scientific reports 2016-03, Vol.6 (1), p.23796-23796, Article 23796
• Main Authors: Guillou, Clément, Fréret, Manuel, Fondard, Emeline, Derambure, Céline, Avenel, Gilles, Golinski, Marie-Laure, Verdet, Mathieu, Boyer, Olivier, Caillot, Frédérique, Musette, Philippe, Lequerré, Thierry, Vittecoq, Olivier
• Format: Article
• Language: English
• Subjects: 13/1; 13/106; 13/31; 38; 38/39; 38/90; 631/250/38; 692/4023/1670/498; 82/80; Animals; Antibodies; Antigens; Autoantibodies; Autoantigens; Biochemistry, Molecular Biology; Biomarkers, Tumor - physiology; Cattle; CD14 antigen; Cells, Cultured; Chemokines; DNA-Binding Proteins - physiology; Enzyme-linked immunosorbent assay; Flow cytometry; Genomics; Humanities and Social Sciences; Humans; Immune system; Inflammation; Innate immunity; Interleukin 10; Interleukin-10 - biosynthesis; Leukocytes (mononuclear); Leukocytes, Mononuclear - enzymology; Life Sciences; Lipopolysaccharide Receptors - metabolism; Lipopolysaccharides - pharmacology; Monocytes; multidisciplinary; Peripheral blood mononuclear cells; Phosphopyruvate hydratase; Phosphopyruvate Hydratase - physiology; Rheumatoid arthritis; Science; Signal Transduction; TLR4 protein; Toll-Like Receptor 4 - metabolism; Toll-like receptors; Tumor Necrosis Factor-alpha - biosynthesis; Tumor Suppressor Proteins - physiology
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep23796

Rheumatoid arthritis (RA) is the most common form of chronic inflammatory rheumatism. Identifying auto-antigens targeted by RA auto-antibodies is of major interest. Alpha-enolase (ENO1) is considered to be a pivotal auto-antigen in early RA but its pathophysiologic role remains unknown. The main objective of this study was to investigate the in vitro effects of soluble ENO1 on peripheral blood mononuclear cells (PBMC) from healthy donors and RA patients in order to determine the potential pathogenic role of ENO1. ELISA, transcriptomic analysis, experiments of receptor inhibition and flow cytometry analysis were performed to determine the effect, the target cell population and the receptor of ENO1. We showed that ENO1 has the ability to induce early production of pro-inflammatory cytokines and chemokines with delayed production of IL-10 and to activate the innate immune system. We demonstrated that ENO1 binds mainly to monocytes and activates the CD14-dependent TLR4 pathway both in healthy subjects and in RA patients. Our results establish for the first time that ENO1 is able to activate in vitro the CD14-dependent TLR4 pathway on monocytes involving a dual mechanism firstly pro-inflammatory and secondly anti-inflammatory. These results contribute to elucidating the role of this auto-antigen in the pathophysiologic mechanisms of RA.