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

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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, I
  • Liu, H
  • Koscik, C
  • Bartczak, A
  • Javadi, M
  • Wong, KM
  • Maknojia, A
  • He, W
  • Liu, MF
  • Diao, J
  • Winter, E
  • Manuel, J
  • McCarthy, D
  • Cattral, M
  • Gommerman, J
  • Clark, David Alexander
  • Phillips, MJ
  • Gorczynski, RR
  • Zhang, L
  • Downey, G
  • Grant, D
  • Cybulsky, MI
  • Levy, G

publication date

  • January 1, 2008