FasL incapacitation alleviates CD4+ T cells-induced brain injury through remodeling of microglia polarization in mouse ischemic stroke

J Neuroimmunol. 2018 May 15:318:36-44. doi: 10.1016/j.jneuroim.2018.01.017. Epub 2018 Feb 1.

Abstract

Inflammation responses involving the crosstalk between infiltrated T cells and microglia play crucial roles in ischemia stroke. Recent studies showed that Fas ligand (FasL) mutation could reduce post-stroke T cell invasion and microglia activation. In this study, we demonstrated that CD4+ T cells could induce M1 microglia polarization through NF-κB signaling pathway, whereas FasL mutant CD4+ T cells significantly reversed this effect. Besides, Th17/Treg cells balance was skewed into Treg cells after FasL mutation. In addition, conditioned medium from co-culture of FasL mutant CD4+ T cells and microglia could alleviate neuronal injury. Collectively, FasL incapacitation could alleviate CD4+ T cells-induced inflammation through remodeling microglia polarization, suggesting a therapeutic potential for control of inflammation responses after ischemic stroke.

Keywords: CD4(+) T cells; Fas ligand; Ischemic stroke; Microglia; NF-κB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Differentiation / immunology
  • Fas Ligand Protein / immunology
  • Fas Ligand Protein / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Microglia / immunology
  • Microglia / pathology*
  • NF-kappa B / metabolism
  • Signal Transduction / physiology
  • Stroke / immunology
  • Stroke / metabolism*
  • Stroke / pathology

Substances

  • Fas Ligand Protein
  • Fasl protein, mouse
  • NF-kappa B