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Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 1/2015

Open Access 01-12-2015 | Research article

Transforming growth factor-β increases interleukin-13 synthesis via GATA-3 transcription factor in T-lymphocytes from patients with systemic sclerosis

Authors: Julie Baraut, Dominique Farge, Francette Jean-Louis, Ingrid Masse, Elena Ivan Grigore, Lucas C. M. Arruda, Jérôme Lamartine, Franck Verrecchia, Laurence Michel

Published in: Arthritis Research & Therapy | Issue 1/2015

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Abstract

Introduction

Transforming growth factor (TGF)-β and interleukin (IL)-13 play a crucial role in the pathogenesis of systemic sclerosis (SSc), partly through activation of collagen production that leads to fibrosis. The aim of the present study was to determine whether TFG-β alters IL-13 production in T lymphocytes from patients with SSc from that seen in those of healthy donors.

Methods

IL-13 mRNA and protein synthesis under TFG-β exposure was measured in circulating T lymphocytes from healthy donors and patients with SSc and also in the Jurkat Th2 T-cell line, using quantitative real-time PCR and fluorescence-activated cell sorting analysis, respectively. The involvement of Smad and GATA-3 transcription factors was assessed by using specific inhibitors and small interfering RNA, and the binding capacity of GATA-3 to the IL-13 gene promoter was evaluated by chromatin immunoprecipitation assay.

Results

TGF-β induced a significant decrease in IL-13 mRNA and protein levels in lymphocytes from healthy donors (mean [±SD] inhibition of 30 % ± 10 % and 20 % ± 7 %, respectively; p < 0.05). In contrast, TGF-β promoted a significant increase in IL-13 mRNA levels and IL-13 synthesis by CD4+ and CD8+ T-cell subtypes from patients with SSc, with respective increases of 2.4 ± 0.3-fold, 1.6 ± 0.05-fold and 2.7 ± 0.02-fold. The involvement of the Smad signaling pathway and upregulation of GATA-3 binding capacity on the IL-13 promoter in lymphocytes from patients with SSc contributed to the effect of TGF-β on IL-13 production.

Conclusions

These results demonstrate that TGF-β upregulates IL-13 synthesis through GATA-3 expression in the T lymphocytes of patients with SSc, confirming that the GATA-3 transcription factor can be regarded as a novel therapeutic target in patients with SSc.
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Metadata
Title
Transforming growth factor-β increases interleukin-13 synthesis via GATA-3 transcription factor in T-lymphocytes from patients with systemic sclerosis
Authors
Julie Baraut
Dominique Farge
Francette Jean-Louis
Ingrid Masse
Elena Ivan Grigore
Lucas C. M. Arruda
Jérôme Lamartine
Franck Verrecchia
Laurence Michel
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2015
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/s13075-015-0708-0

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