The therapeutic potential of toll-like receptor 7 stimulation in Asthma

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Asthma is an inflammatory disorder of the airways frequently characterized by an excessive Th2 adaptive immune response. Activation of Toll-like receptor (TLR)-7, a single-stranded viral RNA receptor that is highly expressed in the airways, triggers a rapid innate immune response and favors a subsequent Th1 response. Because of this role in pulmonary immunoregulation, TLR7 has gained considerable interest as a therapeutic target in asthma. Synthetic TLR7 ligands, including the imidazoquinolines imiquimod (R837) and resiquimod (R848), and 8-hydroxyadenine derivatives have been developed for other clinical indications. TLR7 activation prevents ovalbumin-induced airway hyperreactivity, eosinophilic inflammation, goblet cell hyperplasia and airway remodeling in murine models of asthma. TLR7 activation also inhibits viral replication in the lung and prevents virus-induced airway hyperreactivity. Furthermore, it has recently been shown that stimulating TLR7 rapidly relaxes airway smooth muscle, dilating the airways. This bronchodilating effect, which occurs in seconds to minutes and depends on rapid production of nitric oxide, indicates that TLR7 can signal via previously unrecognized pathways. The effects of decreasing the allergic Th2 response, acting as an immediate bronchodilator, and promoting an antiviral immune environment, make TLR7 an attractive drug target. We examine the current understanding of TLR7 as a therapeutic target and its translation to asthma treatment in humans.

Original languageEnglish (US)
Pages (from-to)484-491
Number of pages8
JournalInflammation and Allergy - Drug Targets
Volume11
Issue number6
DOIs
StatePublished - 2012

Fingerprint

Toll-Like Receptor 7
imiquimod
resiquimod
Asthma
Airway Remodeling
Lung
Goblet Cells
Bronchodilator Agents
Ovalbumin
Viral RNA
Adaptive Immunity
Therapeutics
Innate Immunity
Hyperplasia
Antiviral Agents
Smooth Muscle
Nitric Oxide
Ligands
Viruses
Inflammation

Keywords

  • Asthma
  • Bronchodilator
  • Inflammation
  • Toll-like receptor 7

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Pharmacology

Cite this

The therapeutic potential of toll-like receptor 7 stimulation in Asthma. / Drake, Matthew; Kaufman, Elad H.; Fryer, Allison; Jacoby, David.

In: Inflammation and Allergy - Drug Targets, Vol. 11, No. 6, 2012, p. 484-491.

Research output: Contribution to journalArticle

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