1. Pro-resolving lipid mediator lipoxin A 4 attenuates neuro-inflammation by modulating T cell responses and modifies the spinal cord lipidome.
- Author
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Derada Troletti C, Enzmann G, Chiurchiù V, Kamermans A, Tietz SM, Norris PC, Jahromi NH, Leuti A, van der Pol SMA, Schouten M, Serhan CN, de Vries HE, Engelhardt B, and Kooij G
- Subjects
- Adult, Animals, Brain pathology, Cell Movement drug effects, Cytokines metabolism, Encephalomyelitis, Autoimmune, Experimental immunology, Encephalomyelitis, Autoimmune, Experimental pathology, Female, Humans, Lipoxins chemistry, Mice, Inbred C57BL, Multiple Sclerosis immunology, Multiple Sclerosis pathology, Spinal Cord drug effects, T-Lymphocytes drug effects, Th1 Cells drug effects, Th1 Cells immunology, Th17 Cells drug effects, Th17 Cells immunology, Mice, Brain immunology, Inflammation immunology, Inflammation metabolism, Lipidomics, Lipoxins pharmacology, Spinal Cord metabolism, Spinal Cord pathology, T-Lymphocytes immunology
- Abstract
The chronic neuro-inflammatory character of multiple sclerosis (MS) suggests that the natural process to resolve inflammation is impaired. This protective process is orchestrated by specialized pro-resolving lipid mediators (SPMs), but to date, the role of SPMs in MS remains largely unknown. Here, we provide in vivo evidence that treatment with the SPM lipoxin A
4 (LXA4 ) ameliorates clinical symptoms of experimental autoimmune encephalomyelitis (EAE) and inhibits CD4+ and CD8+ T cell infiltration into the central nervous system (CNS). Moreover, we show that LXA4 potently reduces encephalitogenic Th1 and Th17 effector functions, both in vivo and in isolated human T cells from healthy donors and patients with relapsing-remitting MS. Finally, we demonstrate that LXA4 affects the spinal cord lipidome by significantly reducing the levels of pro-inflammatory lipid mediators during EAE. Collectively, our findings provide mechanistic insight into LXA4 -mediated amelioration of neuro-inflammation and highlight the potential clinical application of LXA4 for MS., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2021
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