Pro-resolving lipid mediator lipoxin A 4 attenuates neuro-inflammation by modulating T cell responses and modifies the spinal cord lipidome

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.