TLRs, future potential therapeutic targets for RA

Hatem A. Elshabrawy, Abdul E. Essani, Zoltán Szekanecz, David A. Fox, Shiva Shahrara

Research output: Contribution to journalReview article

42 Citations (Scopus)

Abstract

Toll like receptors (TLR)s have a central role in regulating innate immunity and in the last decade studies have begun to reveal their significance in potentiating autoimmune diseases such as rheumatoid arthritis (RA). Earlier investigations have highlighted the importance of TLR2 and TLR4 function in RA pathogenesis. In this review, we discuss the newer data that indicate roles for TLR5 and TLR7 in RA and its preclinical models. We evaluate the pathogenicity of TLRs in RA myeloid cells, synovial tissue fibroblasts, T cells, osteoclast progenitor cells and endothelial cells. These observations establish that ligation of TLRs can transform RA myeloid cells into M1 macrophages and that the inflammatory factors secreted from M1 and RA synovial tissue fibroblasts participate in TH-17 cell development. From the investigations conducted in RA preclinical models, we conclude that TLR-mediated inflammation can result in osteoclastic bone erosion by interconnecting the myeloid and TH-17 cell response to joint vascularization. In light of emerging unique aspects of TLR function, we summarize the novel approaches that are being tested to impair TLR activation in RA patients.

Original languageEnglish
Pages (from-to)103-113
Number of pages11
JournalAutoimmunity Reviews
Volume16
Issue number2
DOIs
Publication statusPublished - Feb 1 2017

Keywords

  • Bone erosion
  • Inflammation
  • M1 macrophages
  • Rheumatoid arthritis (RA)
  • TH-17 cells
  • Toll like receptors (TLR)s

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Elshabrawy, H. A., Essani, A. E., Szekanecz, Z., Fox, D. A., & Shahrara, S. (2017). TLRs, future potential therapeutic targets for RA. Autoimmunity Reviews, 16(2), 103-113. https://doi.org/10.1016/j.autrev.2016.12.003