TACI-dependent APRIL signaling maintains autoreactive B cells in a mouse model of systemic lupus erythematosus.

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State: Public
Version: Author's accepted manuscript
Serval ID
serval:BIB_FBC738246962
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
TACI-dependent APRIL signaling maintains autoreactive B cells in a mouse model of systemic lupus erythematosus.
Journal
European journal of immunology
Author(s)
Tran N.L., Schneider P., Santiago-Raber M.L.
ISSN
1521-4141 (Electronic)
ISSN-L
0014-2980
Publication state
Published
Issued date
04/2017
Peer-reviewed
Oui
Volume
47
Number
4
Pages
713-723
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Autoantibodies contribute to the development of systemic lupus erythematosus (SLE). APRIL (a proliferation-inducing ligand), a member of the TNF superfamily, regulates plasma-cell survival and binds to TACI (transmembrane activator CAML interactor) and BCMA (B-cell maturation antigen). We previously showed that APRIL blockade delayed disease onset in lupus-prone mice. In order to evaluate the role of APRIL receptors in the development of SLE, APRIL, TACI, BCMA, or double TACI.BCMA null mutations were introduced into the Nba2.Yaa (Y-linked autoimmune acceleration) spontaneous lupus mouse model. Mortality as a consequence of glomerulonephritis (GN) was reduced in Nba2.APRIL(-/-) .Yaa, Nba2.TACI(-/-) .Yaa and double-KO mice compared with Nba2.Yaa mice and correlated with lower levels of circulating antibodies, while splenic populations remained unchanged. In contrast, the appearance of symptoms was accelerated in BCMA-deficient mice, in which TACI signaling was increased. Finally, lupus-prone mice deficient for the APRIL-TACI axis produced less pathogenic antibodies and developed less GN. Disease reduction was attributed to impaired T-independent type 2 responses when the APRIL-TACI signaling axis was disrupted. Collectively, our results have identified and confirmed APRIL as a new target involved in B-cell activation, in the maintenance of plasma cell survival and subsequent increased autoantibody production that sustains lupus development in mice.

Keywords
Animals, Autoantibodies/metabolism, Autoantigens/immunology, B-Cell Maturation Antigen/genetics, B-Cell Maturation Antigen/metabolism, B-Lymphocytes/immunology, Cells, Cultured, Disease Models, Animal, Disease Susceptibility, Humans, Lupus Erythematosus, Systemic/immunology, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Mutant Strains, Signal Transduction/genetics, Transmembrane Activator and CAML Interactor Protein/genetics, Transmembrane Activator and CAML Interactor Protein/metabolism, Tumor Necrosis Factor Ligand Superfamily Member 13/genetics, Tumor Necrosis Factor Ligand Superfamily Member 13/metabolism, APRIL, B-cell maturation antigen (BCMA), Systemic lupus erythematosus (SLE), TACI, mouse model
Pubmed
Web of science
Open Access
Yes
Create date
14/03/2017 10:42
Last modification date
20/08/2019 16:26
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