title: 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: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immunopharmacology of Education Ministry of China, Hefei 230032, China. q-q2456@163.com
authors: Qiong
authors: Q
authors: Qin
authors: Yan
authors: Y
authors: Chang
authors: Di
authors: D
authors: Wang
authors: Yujing
authors: Y
authors: Wu
authors: Ling-Ling
authors: LL
authors: Zhang
authors: Wei
authors: W
authors: Wei
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000276:immunology*; D053265:B-Cell Activation Factor Receptor / Q000276:immunology; D053301:B-Cell Maturation Antigen / Q000276:immunology; D016207:Cytokines / Q000032:analysis / Q000276:immunology; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology*; D016896:Treatment Outcome; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000276:immunology
chemical_list: D053265:B-Cell Activation Factor Receptor; D053301:B-Cell Maturation Antigen; C120197:BLyS receptor; D016207:Cytokines; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; C524618:TACI receptor-IgG Fc fragment fusion protein