Open AccessStat3 promotes IL-10 expression in lupus T cells through trans- activation and chromatin remodeling
Author(s) -
Christian M. Hedrich,
Thomas Rauen,
Sokratis A. Apostolidis,
Alexandros Grammatikos,
Noé RodríguezRodríguez,
Christina Ioannidis,
Vasileios C. Kyttaris,
José C. Crispín,
George C. Tsokos
Publication year - 2014
Publication title -
proceedings of the national academy of sciences
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.1408023111
Subject(s) - biology , cytokine , epigenetics , interleukin 10 , immunology , stat5 , chromatin remodeling , dna methylation , chromatin , immune system , systemic lupus erythematosus , regulation of gene expression , gene expression , microbiology and biotechnology , signal transduction , medicine , genetics , gene , disease
Significance IL-10 is an immune-regulatory cytokine with pro- and anti-inflammatory functions. Through its B cell-stimulating capacities, IL-10 contributes to the differentiation, activation and survival of B cells. Thus, it has been linked with autoimmune disorders, including systemic lupus erythematosus (SLE). Here, we demonstrate T cells as a source of increased IL-10 expression in SLE. Reduced DNA methylation of theIL10 gene allows for transcription-factor recruitment. Increased phosphorylation of the transcription factor Stat3 in SLE T cells results in epigenetic remodeling andtrans -activation ofIL10 , allowing for IL-10 expression. Thus, our observations offer molecular targets in the search for pathophysiologic mechanisms and target-directed treatment options in SLE.
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