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

Autor: Ngoc Lan Tran, Pascal Schneider, Marie-Laure Santiago-Raber
Rok vydání: 2017
Předmět:
Male
0301 basic medicine
Transmembrane Activator and CAML Interactor Protein
Tumor Necrosis Factor Ligand Superfamily Member 13
Immunology
ddc:616.07
Biology
Plasma cell
Autoantigens
Mouse model
Mice
03 medical and health sciences
Antigen
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
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
medicine
Lupus Erythematosus
Systemic
Immunology and Allergy
B-Cell Maturation Antigen
Receptor
Autoantibodies
B-Lymphocytes
Lupus erythematosus
Systemic lupus erythematosus
Autoantibody
Glomerulonephritis
medicine.disease
030104 developmental biology
medicine.anatomical_structure
biology.protein
Antibody
Signal Transduction
Zdroj: European Journal of Immunology, Vol. 47, No 4 (2017) pp. 713-723
European journal of immunology, vol. 47, no. 4, pp. 713-723
Eur J Immunol
ISSN: 0014-2980
DOI: 10.1002/eji.201646630
Popis: 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.
Databáze: OpenAIRE
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