serval:BIB_FBC738246962
TACI-dependent APRIL signaling maintains autoreactive B cells in a mouse model of systemic lupus erythematosus.
10.1002/eji.201646630
000398808900014
28267197
Tran
N.L.
author
Schneider
P.
author
Santiago-Raber
M.L.
author
article
2017-04
European journal of immunology
1521-4141
0014-2980
journal
47
4
713-723
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.
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
eng
60_published
true
peer-reviewed
Publication types: Journal Article
Publication Status: ppublish
University of Lausanne
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