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

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


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.

Keywords: EAE; SPMs; T cells; central nervous system; experimental autoimmune encephalomyelitis; lipidomics; lipoxin A(4); multiple sclerosis; neuro-inflammation; resolution of inflammation; specialized pro-resolving lipid mediators; spinal cord.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Brain / immunology*
  • Brain / pathology
  • Cell Movement / drug effects
  • Cytokines / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Female
  • Humans
  • Inflammation / immunology*
  • Inflammation / metabolism*
  • Lipidomics*
  • Lipoxins / chemistry
  • Lipoxins / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / pathology
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism*
  • Spinal Cord / pathology*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • Th1 Cells / drug effects
  • Th1 Cells / immunology
  • Th17 Cells / drug effects
  • Th17 Cells / immunology


  • Cytokines
  • Lipoxins
  • lipoxin A4