Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CD11b Antigen / genetics
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Central Nervous System / metabolism
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Central Nervous System / pathology
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Encephalomyelitis, Autoimmune, Experimental / blood
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Encephalomyelitis, Autoimmune, Experimental / genetics*
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Encephalomyelitis, Autoimmune, Experimental / physiopathology
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Gene Deletion
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Gene Expression / genetics
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Humans
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Lysophospholipids / biosynthesis
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Lysophospholipids / genetics*
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Macrophages / metabolism
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Macrophages / pathology
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Mice
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Microglia / metabolism
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Microglia / pathology
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Multiple Sclerosis / blood
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Multiple Sclerosis / genetics*
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Multiple Sclerosis / physiopathology
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Phosphoric Diester Hydrolases / genetics*
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Signal Transduction / genetics
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Spinal Cord / metabolism
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Spinal Cord / physiopathology
Substances
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CD11b Antigen
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Lysophospholipids
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Phosphoric Diester Hydrolases
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alkylglycerophosphoethanolamine phosphodiesterase
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lysophosphatidic acid
Grants and funding
This work has been co‐financed by the European Union and Greek national funds through the Operational Program Competitiveness, Entrepreneurship and Innovation, under the call Research – Create – Innovate (project code: T1EDK-0049). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.