Administration of Maresin-1 ameliorates the physiopathology of experimental autoimmune encephalomyelitis
Sánchez Fernández, Alba (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Zandee, Stephanie (Université de Montréal and Neuroimmunology Unit. Centre de Recherche du CHUM (CRCHUM). Department of Neuroscience.)
Mastrogiovanni, Mauricio (Universidad de La República. Departamento de Bioquímica. Facultad de Medicina y Centro de Investigaciones Biomédicas (CEINBIO))
Charabati, Marc (Université de Montréal and Neuroimmunology Unit. Centre de Recherche du CHUM (CRCHUM). Department of Neuroscience. Faculty of Medicine)
Rubbo, Homero (Universidad de La República. Departamento de Bioquímica. Facultad de Medicina and Centro de Investigaciones Biomédicas (CEINBIO))
Prat, Alexandre (Université de Montréal and Neuroimmunology Unit. Centre de Recherche du CHUM (CRCHUM). Department of Neuroscience. Faculty of Medicine)
López Vales, Rubén (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)

Data:	2022
Resum:	Resolution of inflammation is an active and regulated process that leads to the clearance of cell debris and immune cells from the challenged tissue, facilitating the recovery of homeostasis. This physiological response is coordinated by endogenous bioactive lipids known as specialized pro-resolving mediators (SPMs). When resolution fails, inflammation becomes uncontrolled leading chronic inflammation and tissue damage, as occurs in multiple sclerosis (MS). SPMs and the key biosynthetic enzymes involved in SPM production were analysed by metabololipidomics and qPCR in active brain lesions, serum and peripheral blood mononuclear cells (PBMC) of MS patients as well as in the spinal cord of mice with experimental autoimmune encephalomyelitis (EAE). We also tested the therapeutic actions of the SPM coined Maresin-1 (MaR1) in EAE mice and studied its impact on inflammation by doing luminex and flow cytometry analysis. We show that levels of MaR1 and other SPMs were below the limit of detection or not increased in the spinal cord of EAE mice, whereas the production of pro-inflammatory eicosanoids was induced during disease progression. Similarly, we reveal that SPMs were undetected in serum and active brain lesion samples of MS patients, which was linked to impaired expression of the enzymes involved in the biosynthetic pathways of SPMs. We demonstrate that exogenous administration of MaR1 in EAE mice suppressed the protein levels of various pro-inflammatory cytokines and reduced immune cells counts in the spinal cord and blood. MaR1 also decreased the numbers of Th1 cells but increased the accumulation of regulatory T cells and drove macrophage polarization towards an anti-inflammatory phenotype. Importantly, we provide clear evidence that administration of MaR1 in mice with clinical signs of EAE enhanced neurological outcomes and protected from demyelination. This study reveals that there is an imbalance in the production of SPMs in MS patients and in EAE mice, and that increasing the bioavailability of SPMs, such as MaR1, minimizes inflammation and mediates therapeutic actions. Thus, these data suggest that immunoresolvent therapies, such as MaR1, could be a novel avenue for the treatment of MS. The online version contains supplementary material available at 10. 1186/s12974-022-02386-1.
Ajuts:	Ministerio de Economía y Competitividad SAF2016-79774-R "la Caixa" Foundation LCF/PR/HA17/52170001 Ministerio de Ciencia, Innovación y Universidades PID2020-120267RB-I00
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Experimental autoimmune encephalomyelitis ; Inflammation ; Maresin-1 ; Multiple Sclerosis ; Resolution of inflammation ; Specialized pro-resolving mediators
Publicat a:	Journal of neuroinflammation, Vol. 19 (february 2022) , ISSN 1742-2094

DOI: 10.1186/s12974-022-02386-1
PMID: 35109863

18 p, 4.5 MB

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