Targeted Deletion of fgl2 Leads to Impaired Regulatory T Cell Activity and Development of Autoimmune Glomerulonephritis Academic Article uri icon

  •  
  • Overview
  •  
  • Research
  •  
  • Identity
  •  
  • Additional Document Info
  •  
  • View All
  •  

abstract

  • Mice with targeted deletion of fibrinogen-like protein 2 (fgl2) spontaneously developed autoimmune glomerulonephritis with increasing age, as did wild-type recipients reconstituted with fgl2-/- bone marrow. These data implicate FGL2 as an important immunoregulatory molecule and led us to identify the underlying mechanisms. Deficiency of FGL2, produced by CD4+CD25+ regulatory T cells (Treg), resulted in increased T cell proliferation to lectins and alloantigens, Th 1 polarization, and increased numbers of Ab-producing B cells following immunization with T-independent Ags. Dendritic cells were more abundant in fgl2-/- mice and had increased expression of CD80 and MHCII following LPS stimulation. Treg cells were also more abundant in fgl2-/- mice, but their suppressive activity was significantly impaired. Ab to FGL2 completely inhibited Treg cell activity in vitro. FGL2 inhibited dendritic cell maturation and induced apoptosis of B cells through binding to the low-affinity FcgammaRIIB receptor. Collectively, these data suggest that FGL2 contributes to Treg cell activity and inhibits the development of autoimmune disease.

authors

  • Shalev, Itay
  • Liu, Hao
  • Koscik, Cheryl
  • Bartczak, Agata
  • Javadi, Mojib
  • Wong, Kit Man
  • Maknojia, Asif
  • He, Wei
  • Liu, Ming Feng
  • Diao, Jun
  • Winter, Erin
  • Manuel, Justin
  • McCarthy, Doug
  • Cattral, Mark
  • Gommerman, Jennifer
  • Clark, David Alexander
  • Phillips, M James
  • Gorczynski, Reginald R
  • Zhang, Li
  • Downey, Greg
  • Grant, David
  • Cybulsky, Myron I
  • Levy, Gary

publication date

  • January 1, 2008