TACI-Ig induces immune balance of Th cells in MLN via BLyS/APRIL-receptors signaling in rats with adjuvant-induced arthritis.

Abstract

The transmembrane activator and calcium modulator and cyclophilin ligand interactor-immunoglobulin (TACI-Ig), a recombinant fusion protein that modulates B and T cells activation by binding and neutralizing B lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL), has been shown to have a therapeutic effects on autoimmune disorders. The objective of this study was to investigate immunoregulatory efficacy of TACI-Ig on helper T (Th) cells in mesenteric lymph node (MLN) of adjuvant-induced arthritis (AA) in rats. The levels of BLyS, APRIL, interferon (IFN)-γ, interleukin (IL)-4, transforming growth factor beta (TGF)-β1, and IL-17 were measured by enzyme-linked immunosorbent assay. The localization and expression of TACI, B-cell maturation antigen (BCMA) and B cell activating factor-receptor (BAFF-R) were investigated by immunohistochemistry and western blotting analysis in MLN. Administration of TACI-Ig significantly reduced histological changes, along with decreased Th1 and Th17-cell cytokines and increased CD4(+)CD25(+)FOXP3(+) regulatory T cell (Treg) and Th2-cell cytokines in MLN of AA rats. The levels of BLyS and APRIL were decreased in MLN homogenate of AA rats after treatment with TACI-Ig. TACI-Ig inhibited TACI and BCMA expression, and increased BAFF-R expression in MLN with AA rats. Taken together, BLyS/APRIL-receptors signaling are important not only for B cell function but for T cell-mediated immune responses. TACI-Ig might exert its anti-inflammatory and immunoregulatory effects through inducing immune balance of Th1/Th2 and Treg/Th17 in peripheral MLN. The mechanisms of TACI-Ig on BLyS/APRIL-receptors-dependent signaling in MLN lymphocytes may play key roles in the pathogenesis of autoimmune disorders.

• Authors: Qiong Qin, Yan Chang, Di Wang, Yujing Wu, Ling-Ling Zhang, Wei Wei
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 11 Issue 12 Pg. 2167-75 (Dec 2011) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 21996540 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier B.V. All rights reserved.

Chemical References

• B-Cell Activation Factor Receptor
• B-Cell Maturation Antigen
• BLyS receptor
• Cytokines
• Receptors, Tumor Necrosis Factor
• Recombinant Fusion Proteins
• Tumor Necrosis Factor Ligand Superfamily Member 13
• TACI receptor-IgG Fc fragment fusion protein

Topics

• Animals
• Arthritis, Experimental (drug therapy, immunology)
• B-Cell Activation Factor Receptor (immunology)
• B-Cell Maturation Antigen (immunology)
• Cytokines (analysis, immunology)
• Lymph Nodes (drug effects, immunology)
• Male
• Rats
• Rats, Sprague-Dawley
• Receptors, Tumor Necrosis Factor (immunology)
• Recombinant Fusion Proteins (administration & dosage)
• Signal Transduction (drug effects, immunology)
• T-Lymphocytes, Helper-Inducer (drug effects, immunology)
• Treatment Outcome
• Tumor Necrosis Factor Ligand Superfamily Member 13 (immunology)