Pro-resolving lipid mediator lipoxin A4attenuates 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 vivoevidence 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 LXA4potently reduces encephalitogenic Th1 and Th17 effector functions, both in vivoand in isolated human T cells from healthy donors and patients with relapsing-remitting MS. Finally, we demonstrate that LXA4affects 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 LXA4for MS.