Specialized differentially pro-resolving altered in peripheral lipid mediators blood of patients with multiple sclerosis and attenuate monocyte and blood-brain barrier dysfunction

Gijs Kooij, Claudio Derada Troletti, Alessandro Leuti, Paul C Norris, Ian Riley, Maria Albanese, Serena Ruggieri, Stephania Libreros, Susanne M A van der Pol, Bert van Het Hof, Yoëlle Schell, Gisella Guerrera, Fabio Buttari, Nicola Biagio Mercuri, Diego Centonze, Claudio Gasperini, Luca Battistini, Helga E de Vries, Charles N Serhan, Valerio Chiurchiù

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Chronic inflammation is a key pathological hallmark of multiple sclerosis and suggests that resolution of inflammation, orchestrated by specialized pro-resolving lipid mediators, is impaired. Here, through targeted-metabololipidomics in peripheral blood of patients with multiple sclerosis, we revealed that each disease form was associated with distinct lipid mediator profiles that significantly correlated with disease severity. In particular, relapsing and progressive multiple sclerosis patients were associated with high eicosanoids levels, whereas the majority of pro-resolving lipid mediators were significantly reduced or below limits of detection and correlated with disease progression. Furthermore, we found impaired expression of several pro-resolving lipid mediators biosynthetic enzymes and receptors in blood-derived leukocytes of MS patients. Mechanistically, differentially expressed mediators like LXA4, LXB4, RvD1 and PD1 reduced multiple sclerosis-derived monocyte activation and cytokine production and inhibited inflammation-induced blood-brain barrier dysfunction and monocyte transendothelial migration. Altogether, these findings reveal peripheral defects in the resolution pathway in multiple sclerosis, suggesting pro-resolving lipid mediators as novel diagnostic biomarkers and potentially safe therapeutics.

Original languageEnglish
Pages (from-to)2056-2070
Number of pages15
JournalHaematologica
Volume105
Issue number8
DOIs
Publication statusPublished - 1 Aug 2020

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