TY  - JOUR
A1  - Schmitz, Katja
A1  - Brunkhorst, Robert
A1  - Bruin, Natasja de
A1  - Mayer, Christoph
A1  - Häussler, Annett
A1  - Ferreirós Bouzas, Nerea
A1  - Schiffmann, Susanne
A1  - Parnham, Michael J.
A1  - Tunaru, Sorin
A1  - Chun, Jerold
A1  - Offermanns, Stefan
A1  - Förch, Christian
A1  - Scholich, Klaus
A1  - Vogt, Johannes
A1  - Wicker, Sabine
A1  - Lötsch, Jörn
A1  - Geisslinger, Gerd
A1  - Tegeder, Irmgard
T1  - Dysregulation of lysophosphatidic acids in multiple sclerosis and autoimmune encephalomyelitis
T2  - Acta Neuropathologica Communications
N2  - Bioactive lipids contribute to the pathophysiology of multiple sclerosis. Here, we show that lysophosphatidic acids (LPAs) are dysregulated in multiple sclerosis (MS) and are functionally relevant in this disease. LPAs and autotaxin, the major enzyme producing extracellular LPAs, were analyzed in serum and cerebrospinal fluid in a cross-sectional population of MS patients and were compared with respective data from mice in the experimental autoimmune encephalomyelitis (EAE) model, spontaneous EAE in TCR1640 mice, and EAE in Lpar2 -/- mice. Serum LPAs were reduced in MS and EAE whereas spinal cord LPAs in TCR1640 mice increased during the ‘symptom-free’ intervals, i.e. on resolution of inflammation during recovery hence possibly pointing to positive effects of brain LPAs during remyelination as suggested in previous studies. Peripheral LPAs mildly re-raised during relapses but further dropped in refractory relapses. The peripheral loss led to a redistribution of immune cells from the spleen to the spinal cord, suggesting defects of lymphocyte homing. In support, LPAR2 positive T-cells were reduced in EAE and the disease was intensified in Lpar2 deficient mice. Further, treatment with an LPAR2 agonist reduced clinical signs of relapsing-remitting EAE suggesting that the LPAR2 agonist partially compensated the endogenous loss of LPAs and implicating LPA signaling as a novel treatment approach.
KW  - Lysophosphatidic acids
KW  - multiple sclerosis
KW  - Autoimmune encephalomyelitis
KW  - Lpar2
KW  - Neuroinflammation
KW  - Spinal cord
KW  - T-cell homing
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/45605
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-456057
SN  - 2051-5960
N1  - © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
VL  - 5
IS  - 1, Art. 42
SP  - 1
EP  - 18
PB  - Biomed Central
CY  - London
ER  -