Therapeutic targeting of Toll-like receptors: a review of Toll-like receptors and their signaling pathways in psoriasis

Expert Rev Clin Immunol. 2016 Dec;12(12):1289-1298. doi: 10.1080/1744666X.2016.1204232. Epub 2016 Jul 4.

Abstract

Expression of various Toll-like receptors (TLR) in keratinocytes (KCs) has offered new insights into the pathogenesis of psoriasis. When plasmacytoid dendritic cells (pDCs) are scarce in established psoriatic lesions, KCs take the responsibility to secrete IFN type 1 through TLR9 activation. Antagonists of TLR7 and TLR8 and anti-IL-12/IL-23 substances have shown promising results in treating psoriasis. Areas covered: References in this study were extracted from Scopus, PubMed and Embase databases by the search term: ('Toll-Like Receptors' OR 'TLR') AND ('Psoriasis' OR 'Arthritis, Psoriatic' OR 'PsA'). Expert commentary: As the prevailing cell type, KCs play a major role in the maintenance of psoriatic lesions. By specific upregulation of IL-36 R, KCs can start the IL-23/IL-12 axis, leading to production of major culprits of psoriatic phenotype IL-17 and IL-22. Targeting IL-36 R could be considered as a new therapeutic target to eliminate cutaneous manifestations of psoriasis.

Keywords: Toll-like receptors; imiquimod; immunotherapy; psoriasis.

Publication types

  • Review

MeSH terms

  • Aminoquinolines / therapeutic use*
  • Animals
  • Cytokines / metabolism*
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology
  • Humans
  • Imiquimod
  • Keratinocytes / drug effects*
  • Keratinocytes / physiology
  • Molecular Targeted Therapy
  • Psoriasis / drug therapy*
  • Signal Transduction
  • Toll-Like Receptors / metabolism*

Substances

  • Aminoquinolines
  • Cytokines
  • Toll-Like Receptors
  • Imiquimod