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.
N1 - Funding Information:
This work was supported by the National Institutes of Health R01 AI075167 (KAG) and a pre-doctoral research assistantship awarded by the University of Nebraska Medical Center (DET). We thank Kimberly Bynoté for performing the isotype ELISAs. We also thank Jenny Nuxoll for conducting genotyping during backcrossing. We gratefully acknowledge Victoria Smith, Samantha Wall, and Dr. Philip Hexley of the University of Nebraska Medical Center Flow Cytometry Research Facility, who contributed to the acquisition and analysis of flow cytometric data. The UNMC Flow Cytometry Research Facility is administrated through the Office of the Vice Chancellor for Research and supported by state funds from the Nebraska Research Initiative (NRI) and The Fred and Pamela Buffett Cancer Center's National Cancer Institute Cancer Support Grant. Major instrumentation in this facility has been provided by the Office of the Vice Chancellor for Research, The University of Nebraska Foundation, the Nebraska Banker's Fund, and by the NIH-NCRR Shared Instrument Program.
Publisher Copyright:
© 2016 Elsevier Inc.
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
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U2 - 10.1016/j.clim.2016.10.011
DO - 10.1016/j.clim.2016.10.011
M3 - Article
C2 - 27989899
AN - SCOPUS:84997769344
SN - 1521-6616
VL - 174
SP - 41
EP - 52
JO - Clinical Immunology
JF - Clinical Immunology
ER -