A mouse model of systemic lupus erythematosus responds better to soluble TACI than to soluble BAFFR, correlating with depletion of plasma cells.

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State: Serval
Version: Final published version
Serval ID
serval:BIB_40845172BB8D
Type
Article: article from journal or magazin.
Collection
Publications
Title
A mouse model of systemic lupus erythematosus responds better to soluble TACI than to soluble BAFFR, correlating with depletion of plasma cells.
Journal
European Journal of Immunology
Author(s)
Haselmayer P., Vigolo M., Nys J., Schneider P., Hess H.
ISSN
1521-4141 (Electronic)
ISSN-L
0014-2980
Publication state
Published
Issued date
2017
Peer-reviewed
Oui
Volume
47
Number
6
Pages
1075-1085
Language
english
Abstract
The TNF family cytokines B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) support plasma cell survival. It is known that inhibitors of BAFF only (BAFFR-Fc) or BAFF and APRIL (TACI-Fc) administered early enough in an NZB/NZW F1 mouse model of systemic lupus erythematosus (SLE) ameliorate clinical outcomes, pointing to a pathogenic role of BAFF. In the present study, TACI-Fc administrated at a later stage of disease, after onset of autoimmunity, decreased the number of bone marrow plasma cells and slowed down further formation of autoantibodies. TACI-Fc prevented renal damage during a 12-week treatment period regardless of autoantibody levels, while BAFFR-Fc did not despite a similar BAFF-blocking activity in vivo. TACI-Fc also decreased established plasma cells in a T-dependent hapten/carrier immunization system better than single inhibitors of BAFF or APRIL, and sometimes better than combined single inhibitors with at least equivalent BAFF and APRIL inhibitory activities. These results indicate that TACI-Fc can prevent symptoms of renal damage in a mouse model of SLE when BAFFR-Fc cannot, and point to a plasticity of plasma cells for survival factors. Targeting plasma cells with TACI-Fc might be beneficial to prevent autoantibody-mediated damages in SLE.

Keywords
APRIL, BAFF/BLyS, Lupus, Plasma cell, SLE
Pubmed
Web of science
Open Access
Yes
Create date
21/04/2017 10:24
Last modification date
08/05/2019 17:37
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