Premium
Targeted deletion of fgl2 leads to impaired regulatory T cell activity and development of autoimmune glomerulonephritis
Author(s) -
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,
Gommerman Jennifer,
Cattral Mark,
Clark David A,
Phillips James,
Gorczynski Reginald R,
Zhang Li,
Downey Greg,
Grant David,
Cybulsky Myron I,
Levy Gary
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1073.16
Subject(s) - immunology , antibody , autoimmune disease , biology
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, T helper 1 (Th1) polarization, and increased numbers of antibody‐producing B cells following immunization with T‐independent antigens. Dendritic cells (DC) 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. Antibody to FGL2 completely inhibited Treg cell activity in vitro . FGL2 inhibited DC maturation and induced apoptosis of B cells through binding to the low affinity FcγRIIB receptor. Collectively, these data suggest that FGL2 contributes to Treg cell activity and inhibits the development of autoimmune disease. This work was supported in part by grants from the Heart and Stroke Foundation of Canada and the Canadian Institutes for Health Research.