RT Journal Article
T1 Activation of Macrophages by Lysophosphatidic Acid through the Lysophosphatidic Acid Receptor 1 as a Novel Mechanism in Multiple Sclerosis Pathogenesis.
A1 Fransson, Jennifer
A1 Gómez-Conde, Ana Isabel
A1 Romero-Imbroda, Jesús
A1 Fernández, Oscar
A1 Leyva, Laura
A1 de Fonseca, Fernando Rodríguez
A1 Chun, Jerold
A1 Louapre, Celine
A1 Van-Evercooren, Anne Baron
A1 Zujovic, Violetta
A1 Estivill-Torrús, Guillermo
A1 García-Díaz, Beatriz
K1 Experimental autoimmune encephalomyelitis
K1 Inflammation
K1 LPA1 receptor
K1 Lysophosphatidic acid
K1 Macrophages
K1 Multiple sclerosis
AB Multiple sclerosis (MS) is a neuroinflammatory disease whose pathogenesis remains unclear. Lysophosphatidic acid (LPA) is an endogenous phospholipid involved in multiple immune cell functions and dysregulated in MS. Its receptor LPA1 is expressed in macrophages and regulates their activation, which is of interest due to the role of macrophage activation in MS in both destruction and repair. In this study, we studied the genetic deletion and pharmaceutical inhibition of LPA1 in the mouse MS model, experimental autoimmune encephalomyelitis (EAE). LPA1 expression was analyzed in EAE mice and MS patient immune cells. The effect of LPA and LPA1 on macrophage activation was studied in human monocyte-derived macrophages. We show that lack of LPA1 activity induces milder clinical EAE course and that Lpar1 expression in peripheral blood mononuclear cells (PBMC) correlates with onset of relapses and severity in EAE. We see the same over-expression in PBMC from MS patients during relapse compared with progressive forms of the disease and in stimulated monocyte-derived macrophages. LPA induced a proinflammatory-like response in macrophages through LPA1, providing a plausible way in which LPA and LPA1 dysregulation can lead to the inflammation in MS. These data show a new mechanism of LPA signaling in the MS pathogenesis, prompting further research into its use as a therapeutic target biomarker.
YR 2020
FD 2020-09-24
LK http://hdl.handle.net/10668/16313
UL http://hdl.handle.net/10668/16313
LA en
DS RISalud
RD Apr 11, 2025