1. Brief Report: Etanercept Inhibits the Tumor Necrosis Factor α-Driven Shift of Th17 Lymphocytes Toward a Nonclassic Th1 Phenotype in Juvenile Idiopathic Arthritis.
- Author
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Maggi, Laura, Cimaz, Rolando, Capone, Manuela, Santarlasci, Veronica, Querci, Valentina, Simonini, Gabriele, Nencini, Francesca, Liotta, Francesco, Romagnani, Sergio, Maggi, Enrico, Annunziato, Francesco, and Cosmi, Lorenzo more...
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T cells ,ACADEMIC medical centers ,FLOW cytometry ,POLYMERASE chain reaction ,RESEARCH funding ,JUVENILE idiopathic arthritis ,STATISTICS ,U-statistics ,DATA analysis ,ETANERCEPT ,REVERSE transcriptase polymerase chain reaction ,PHARMACODYNAMICS ,THERAPEUTICS ,PHYSIOLOGY - Abstract
Objective To evaluate the effects of etanercept on the phenotype of CD4+ T helper lymphocytes from patients with juvenile idiopathic arthritis (JIA). Methods We compared the proportions of various Th cell subsets in peripheral blood (PB) from etanercept-treated and untreated JIA patients. An in vitro study was performed on PB mononuclear cells (PBMCs) from 15 children with untreated JIA, in which we evaluated the proliferative response of these cells, as well as their cytokine production profile, in the presence of various stimuli with or without etanercept. Results We found lower proportions of CD4+ CD161+ (nonclassic) Th1 lymphocytes in the PB of patients treated with etanercept than in untreated patients. In vitro, etanercept inhibited the proliferative response induced by either polyclonal or recall antigen stimulation of PBMCs. Moreover, etanercept increased the proportion of CD4+CD161+ Th17/Th1 and Th17 cells in vitro while decreasing the proportions of nonclassic Th1 cell subsets, leaving CD4+CD161− (classic) Th1 cells unaffected. We also found that tumor necrosis factor α (TNFα) was able to induce transition of Th17 lymphocytes toward the nonclassic Th1 phenotype in vitro, probably due to the high expression of TNF receptor type II observed in Th17 cells. Conclusion We have previously demonstrated the occurrence of a shifting of CD4+CD161+ Th17 cells to the nonclassic Th1 phenotype in children with JIA. The present findings suggest that etanercept can exert its disease-modifying action by interfering with this shifting. [ABSTRACT FROM AUTHOR] more...
- Published
- 2014
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