TY - JOUR
T1 - Estrogen receptor alpha promotes lupus in (NZB × NZW)F1 mice in a B cell intrinsic manner
AU - Tabor, Dana E.
AU - Gould, Karen A.
PY - 2017/1/1
Y1 - 2017/1/1
N2 - Lupus is a systemic autoimmune disease characterized by the production of autoreactive antibodies against nuclear antigens. Women are disproportionately affected by lupus, and this sex bias is thought to be due, in large part, to the ability of estrogens to promote lupus pathogenesis. Previously, we have shown that global deletion of estrogen receptor alpha (ERα) significantly attenuated loss of tolerance, immune cell activation, autoantibody production, and the development of lupus nephritis. Here we show that targeted deletion of ERα specifically in B cells retards production of pathogenic autoantibodies and the development of nephritis in lupus-prone (NZB × NZW)F1 mice. Furthermore, we observed that ERα deletion in B cells was associated with decreased B cell activation in young, pre-autoimmune (NZB × NZW)F1 females. Altogether, these data suggest that ERα acts in a B cell-intrinsic manner to control B cell activation, autoantibody production, and lupus nephritis.
AB - Lupus is a systemic autoimmune disease characterized by the production of autoreactive antibodies against nuclear antigens. Women are disproportionately affected by lupus, and this sex bias is thought to be due, in large part, to the ability of estrogens to promote lupus pathogenesis. Previously, we have shown that global deletion of estrogen receptor alpha (ERα) significantly attenuated loss of tolerance, immune cell activation, autoantibody production, and the development of lupus nephritis. Here we show that targeted deletion of ERα specifically in B cells retards production of pathogenic autoantibodies and the development of nephritis in lupus-prone (NZB × NZW)F1 mice. Furthermore, we observed that ERα deletion in B cells was associated with decreased B cell activation in young, pre-autoimmune (NZB × NZW)F1 females. Altogether, these data suggest that ERα acts in a B cell-intrinsic manner to control B cell activation, autoantibody production, and lupus nephritis.
KW - B cell
KW - Estrogen receptor alpha
KW - Immune cell activation
KW - Immunologic tolerance
KW - Lupus
UR - http://www.scopus.com/inward/record.url?scp=84997769344&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84997769344&partnerID=8YFLogxK
U2 - 10.1016/j.clim.2016.10.011
DO - 10.1016/j.clim.2016.10.011
M3 - Article
C2 - 27989899
AN - SCOPUS:84997769344
VL - 174
SP - 41
EP - 52
JO - Clinical Immunology
JF - Clinical Immunology
SN - 1521-6616
ER -