0000000001212668
AUTHOR
A Accardo Palumbo
AUTOPHAGY, BUT NOT THE UNFOLDED PROTEIN RESPONSE, REGULATES THE EXPRESSION OF IL-23 IN THEGUT OF PATIENTS WITH ANKYLOSING SPONDYLITIS AND SUBCLINICAL GUT INFLAMMATION
Background: IL-23 is a heterodimeric cytokine that has been implicated in the pathogenesis of Ankylosing Spondylitis (AS). High serum and tissue levels for this cytokine have been demonstrated in AS and correlated with entheseal inflammation but the mechanisms responsible for its over-expression are currently not clear. Objectives: The aim of the study was to clarify the immunological mechanisms underlying the increased IL-23 expression in the gut of AS patients. Methods: Consecutive gut biopsies from 20 HLA-B27+ AS patients and 10 normal subjects were considered for the present study. The occurrence of HLA-B27 misfolding was studied by assessing the co-localization of HLA-B heavy chains (H…
Phenotype and functional changes of Vgamma9/Vdelta2 T lymphocytes in Behçet's disease and the effect of infliximab on Vgamma9/Vdelta2 T cell expansion, activation and cytotoxicity
INTRODUCTION: Infliximab is a chimeric monoclonal antibody against tumor necrosis factor alpha (TNF-alpha) that has been introduced recently for Behçet's disease (BD) patients who were resistant to standard treatment. The aim of this study was to analyse the functional changes of Vgamma9/Vdelta2 T lymphocytes in both active and inactive disease and the effect of infliximab on Vgamma9/Vdelta2 T cell expansion, activation and cytotoxicity. METHODS: We investigated 1) cell expansion, 2) expression of TNFRII receptor, 3) perforin and gamma interferon (IFN) content, 4) release of granzyme A (GrA) and 5) phenotype changes, in vitro and in vivo, in Vgamma9/Vdelta2 T lymphocytes by means of fluores…
Expansion of intestinal CD4+CD25(high) Treg cells in patients with ankylosing spondylitis: a putative role for interleukin-10 in preventing intestinal Th17 response
Objective: subclinical gut inflammation has been demonstrated in ankylosing spondylitis (AS) patients. Aim of this study was to determine the frequency of regulatory CD4+CD25high T cells (Treg), and to evaluate Treg-related cytokines (IL-2, TGF-β, IL-10), and transcription factors (FOXP3 and STAT5) in the ileum of AS patients. Methods: Quantitative gene expression analysis, by rt-PCR, of Treg-related cytokines (IL-2, TGF-β, IL-10) and transcription factor (STAT-5 and FOXP3) was performed on ileal biopsies of 18 AS and 15 active Crohn’s disease (CD) patients, and 15 healthy subjects (HS). Tissue and circulating Treg cells were also analyzed by flow cytometry. Results: A significant up-regula…
NF-kappaB protects Behcet's disease T cells against CD95-induced apoptosis up-regulating antiapoptotic proteins
OBJECTIVE: To determine whether prolongation of the inflammatory reaction in patients with Behçet's disease (BD) is related to apoptosis resistance and is associated with the up-regulation of antiapoptotic factors. METHODS: The percentage of cell death was evaluated by flow cytometry in peripheral blood mononuclear cells from 35 patients with BD and 30 healthy volunteers. The expression levels of antiapoptotic factors and NF-kappaB regulatory proteins were measured using Western blotting and immunohistochemical analyses. To down-regulate NF-kappaB nuclear translocation, BD T lymphocytes were exposed in vitro to thalidomide and subjected to transfection with NF-kappaB small interfering RNA. …