Toll-like Receptor 7–triggered Immune Response in the Lung Mediates Acute and Long-Lasting Suppression of Experimental Asthma

• DOI: 10.1164/rccm.200908-1255oc
• Publication Date: 2010-03-12T03:25:28Z
• Authors: Charoula Xirakia; Ourania Koltsida; Athanasios Stavro...; Artemis Thanassop...; Vassilis Aidinis; Paschalis Sideras; Evangelos Andreakos
• Keywords: TLR7; Plasmacytoid dendritic cell; TLR3

Rationale: Toll-like receptor (TLR) 7/8 ligands are promising candidate drugs for the treatment of allergic asthma and rhinitis. Although their clinical application depends on development strategies topical administration to lung, this has not been explored in preclinical disease models.Objectives: To examine therapeutic effectiveness, persistence effect, mode action intranasal TLR7 ligand airway disease.Methods: Wild-type, IFN-α (IFN-αR)−/−, IFN-γ−/−, CD8−/−, TLR7−/−, radiation-induced chimeric mice deficient hematopoietic expression were subjected an established model disease. R-848, a specific agonist mice, was administered prophylactically or therapeutically effects helper T-cell type 2 (Th2) responses, eosinophilia, goblet cell metaplasia, hyperresponsiveness assessed.Measurements Main Results: Intranasal R-848 induced transient immune response characterized by I interferon production infiltration innate cells into lung. This conferred long-term suppression via two complementary molecular processes, one mediated interferons providing acute protection directly inhibiting effector Th2 immunoregulatory CD8+ T inducing long-lasting suppressing responses IFN-γ–dependent manner.Conclusions: is effective It hijacks otherwise proinflammatory process triggered mediate suppression. provides important insight efficacy murine models paves way humans.