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

Autor: Philipp Haselmayer, Henry Hess, Michele Vigolo, Josquin Nys, Pascal Schneider
Rok vydání: 2017
Předmět:
0301 basic medicine
Transmembrane Activator and CAML Interactor Protein
Plasma Cells
Tumor Necrosis Factor Ligand Superfamily Member 13
Immunology
SLE
Lupus
Autoimmunity
BAFF/BLyS
Plasma cell
Biology
Kidney
medicine.disease_cause
Mice
03 medical and health sciences
0302 clinical medicine
immune system diseases
B-Cell Activating Factor
medicine
Animals
Lupus Erythematosus
Systemic
Immunology and Allergy
APRIL
Basic
skin and connective tissue diseases
BAFF receptor
B-cell activating factor
Research Articles
Autoantibodies
B-Lymphocytes
Lupus erythematosus
Systemic lupus erythematosus
Autoantibody
Flow Cytometry
medicine.disease
3. Good health
Disease Models
Animal
030104 developmental biology
medicine.anatomical_structure
Immunodeficiencies and autoimmunity
Research Article|Basic
Bone marrow
B-Cell Activation Factor Receptor
030215 immunology
Zdroj: Eur J Immunol
European Journal of Immunology, vol. 47, no. 6, pp. 1075-1085
European Journal of Immunology
ISSN: 0014-2980
Popis: 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.
Databáze: OpenAIRE
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