Increased expression of TLR2 in CD4+ T cells from SLE patients enhances immune reactivity and promotes IL-17 expression through histone modifications

Yu Liu, Jieyue Liao, Ming Zhao, Haijing Wu, Susan Yung, Tak Mao Chan, Akihiko Yoshimura, Qianjin Lu

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

The innate immune system has been shown to play an important pathologic role in systemic lupus erythematosus (SLE). TLR2, a PRR, recognizes exogenous PAMPs, and endogenous damage-associated molecular patterns and has been implicated in the initiation and maintenance of the perpetuated inflammatory reactions in autoimmune diseases. Here, we report increased expression of TLR2 in CD4+ and CD8+ T cells, CD19+ B cells, and CD14+ monocytes from SLE patients. Conventional treatment, such as hydroxychloroquine and corticosteroids, showed no effect on TLR2 expression in CD4+ T cells from SLE patients. In vitro stimulation of TLR2 in CD4+ T cells from SLE patients increased CD40L and CD70 expression, as well as secretion of IL-6, IL-17A, IL-17F, and TNF-α, while Foxp3 transcription decreased. This effect was reversed by TLR2 siRNA. Moreover, TLR2 activation upregulated H3K4 tri-methylation and H4 acetylation levels while downregulated H3K9 tri-methylation level in the IL-17A promoter region. In addition, it also increased H4 acetylation levels and decreased H3K9 tri-methylation levels in the IL-17F promoter region. In summary, our findings demonstrate that increased expression of TLR2 contributes to immune reactivity and promotes IL-17A and IL-17F expression through histone modifications in SLE.

Original languageEnglish
Pages (from-to)2683-2693
Number of pages11
JournalEuropean Journal of Immunology
Volume45
Issue number9
DOIs
Publication statusPublished - 2015 Sep 1

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Keywords

  • Histone modification
  • IL-17
  • Systemic lupus erythematosus
  • T cells
  • TLR2

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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