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10.1186/s12967-016-0846-4

http://scihub22266oqcxt.onion/10.1186/s12967-016-0846-4
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suck abstract from ncbi


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pmid27098560
      J+Transl+Med 2016 ; 14 (ä): 98
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  • Fn14-Fc suppresses germinal center formation and pathogenic B cells in a lupus mouse model via inhibition of the TWEAK/Fn14 Pathway #MMPMID27098560
  • Min HK ; Kim SM ; Park JS ; Byun JK ; Lee J ; Kwok SK ; Park YW ; Cho ML ; Park SH
  • J Transl Med 2016[Apr]; 14 (ä): 98 PMID27098560 show ga
  • BACKGROUND: Systemic 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. METHODS: To 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 (H&E) and periodic acid-Schiff (PAS). RESULTS: Administration 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. CONCLUSION: Fn14-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.
  • |*Signal Transduction [MESH]
  • |Animals [MESH]
  • |B-Lymphocytes/*pathology [MESH]
  • |Cell Differentiation [MESH]
  • |Cytokine TWEAK [MESH]
  • |Disease Models, Animal [MESH]
  • |Germinal Center/*metabolism [MESH]
  • |Immunoglobulins/metabolism [MESH]
  • |Lupus Erythematosus, Systemic/*immunology/*pathology [MESH]
  • |Mice, Inbred C57BL [MESH]
  • |Receptors, Fc/*metabolism [MESH]
  • |Receptors, Tumor Necrosis Factor/*metabolism [MESH]
  • |T-Lymphocytes, Helper-Inducer/metabolism [MESH]
  • |TWEAK Receptor [MESH]


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