Cell Reports 2021 highlights

Title: Pro-resolving lipid mediator Lipoxin A4 attenuates neuro-inflammation by modulating T cell responses and modifies the spinal cord lipidome

Authors: Claudio Derada Troletti, Gaby Enzmann, Valerio Chiurchi├╣, Alwin Kamermans, Silvia Martina Tietz, Paul C. Norris, Neda Haghayegh Jahromi, Alessandro Leuti, Susanne M.A. van der Pol, Marijn Schouten, Charles N. Serhan, Helga E. de Vries, Britta Engelhardt and Gijs Kooij.

Published: June 1st 2021: Cell Rep 2021 Jun 1;35(9):109201. doi: 10.1016/j.celrep.2021.109201.

Summary and key findings:

Multiple sclerosis (MS) is the most common chronic inflammatory disorder of the central nervous system (CNS), characterized by blood-brain barrier disruption, immune cell infiltration into the CNS, demyelination and neurodegeneration. The majority of the current therapies consists of immunosuppressive or anti-inflammatory agents, which are effective in early stages of the disease, but often results in severe side effects and eventually fail to prevent disease progression. Therefore, there is an urgent need to develop alternative approaches allowing not only to interfere with chronic neuro-inflammation, but also to promote local tissue recovery and subsequent homeostasis.

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. In this Cell Reports manuscript, Gijs Kooij and colleagues provide in vivo evidence that treatment with the SPM lipoxin A4 (LXA4) ameliorates clinical symptoms in an animal model for MS (experimental autoimmune encephalomyelitis, EAE) and inhibits CD4+ and CD8+ T cell infiltration into the central nervous system (CNS) during EAE. Moreover, they show that LXA4 potently reduces pathogenic Th1 and Th17 effector functions, both in vivo and in isolated human T cells from healthy donors and patients with relapsing-remitting MS. Finally, they provide a full characterization of the spinal cord lipidome under healthy and EAE conditions and demonstrate that LXA4 normalizes this lipidome by significantly reducing the levels of pro-inflammatory lipid mediators during EAE. Collectively, besides providing critical mechanistic insight into LXA4-mediated amelioration of neuro-inflammation, these findings highlight the potential clinical application of LXA4 for MS.