Open AccessGenetic deletion of Autotaxin from CD11b+ cells decreases the severity of experimental autoimmune encephalomyelitis
Author(s) -
Ioaninou,
Ioanna Sevastou,
Christiana Magkrioti,
Eleanna Kaffe,
George Stamatakis,
Spyros Thivaios,
George Panayotou,
Junken Aoki,
George Kollias,
Vassilis Aidinis
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0226050
Subject(s) - autotaxin , experimental autoimmune encephalomyelitis , lysophosphatidic acid , microglia , encephalomyelitis , immunology , integrin alpha m , autocrine signalling , biology , pathogenesis , microbiology and biotechnology , cancer research , receptor , immune system , inflammation , multiple sclerosis , biochemistry
Autotaxin (ATX) is a secreted lysophospholipase D catalyzing the extracellular production of lysophosphatidic acid (LPA), a growth factor-like signaling lysophospholipid. ATX and LPA signaling have been incriminated in the pathogenesis of different chronic inflammatory diseases and various types of cancer. In this report, deregulated ATX and LPA levels were detected in the spinal cord and plasma of mice during the development of experimental autoimmune encephalomyelitis (EAE). Among the different sources of ATX expression in the inflamed spinal cord, F4/80 + CD11b + cells, mostly activated macrophages and microglia, were found to express ATX, further suggesting an autocrine role for ATX/LPA in their activation, an EAE hallmark. Accordingly, ATX genetic deletion from CD11b + cells attenuated the severity of EAE, thus proposing a pathogenic role for the ATX/LPA axis in neuroinflammatory disorders.