Pro-resolving lipid mediator lipoxin A 4 attenuates neuro-inflammation by modulating T cell responses and modifies the spinal cord lipidome
Creators
- 1. Vrije Universiteit Amsterdam
- 2. University of Bern
- 3. IRCCS Santa Lucia Foundation, CNR of Rome
- 4. Harvard Medical School
- 5. Campus Bio-Medico University of Rome
Description
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 A4 (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.
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Publication 1_Cell rep.pdf
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