Fn14-Fc suppresses germinal center formation and pathogenic B cells in a lupus mouse model via inhibition of the TWEAK-Fn14 PathwayReportar como inadecuado




Fn14-Fc suppresses germinal center formation and pathogenic B cells in a lupus mouse model via inhibition of the TWEAK-Fn14 Pathway - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Journal of Translational Medicine

, 14:98

Immunobiology and immunotherapy

Abstract

BackgroundSystemic lupus erythematosus SLE is an autoimmune-mediated chronic inflammatory disease. Half of patients with SLE suffer from lupus nephritis, which is major cause of death in SLE. TNF-like weak inducer of apoptosis TWEAK-fibroblast growth factor-inducible 14 Fn14 interactions mediate inflammatory responses that are linked to the pathogenesis of lupus nephritis. Blocking of the TWEAK-Fn14 pathway by Fn14-Fc was performed in a SLE mouse model and the likely therapeutic mechanisms were investigated.

MethodsTo investigate the impact of TWEAK on B cell differentiation in SLE, the levels of AID, Blimp-1, and IRF4 messenger RNA were measured in CD19 B cells extracted from the spleens of sanroque mice and cultured with TWEAK. To identify the therapeutic effects of Fn14-Fc in SLE, sanroque mice were treated with Fn14-Fc or a control-Fc for 3 weeks. Immunoglobulin Ig G, IgG1, IgG2a, and anti-dsDNA antibody Ab levels were measured in the sera of each group. Spleens from each group were stained with antibodies against CD4, B220, GL-7, CD138, and PD-1. Kidneys were stained with hematoxylin and eosin HandE and periodic acid-Schiff PAS.

ResultsAdministration of TWEAK increased the mRNA levels of AID, Blimp-1, and IRF4. Treatment with Fn14-Fc suppressed levels of IgG, IgG1, IgG2a, and anti-dsDNA Ab in sera and reduced numbers of B, plasma, and follicular helper T Tfh cells in spleens of sanroque mice. In addition, renal protective effects of Fn14-Fc were shown.

ConclusionFn14-Fc had beneficial effects in a SLE mouse model by repressing B cells, plasma cells, Tfh, and renal damage. This suggested that Fn14-Fc represents a potential therapeutic agent for SLE.

KeywordsTNF-like weak inducer of apoptosis TWEAK Fibroblast growth factor-inducible 14 Fn14 Systemic lupus erythematosus SLE Germinal center GC Follicular helper T Tfh cell Hong-Ki Min and Sung-Min Kim contributed equally to this work. Mi-La Cho and Sung-Hwan Park contributed equally to this work

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Autor: Hong-Ki Min - Sung-Min Kim - Jin-Sil Park - Jae-Kyeong Byun - Jennifer Lee - Seung-Ki Kwok - Young-Woo Park - Mi-La Cho -

Fuente: https://link.springer.com/







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