TLR 7/8 agonist resiquimod alleviates murine allergic asthma through IL-27 production and up regulation of B7-H1 on antigen presenting cells

Background: Counter balancing Th2-cytokine production through enhanced skewing of CD4+ T helper cells into Th1 cells is currently one of the central immunomodulatory approaches for treatment of allergic diseases. Methods: We systemically sensitized mice followed by intranasal challenge with the model allergen. Resiquimod was administered intranasally before the challenge period. Airway inflammation, antigen-specific immunoglobulins and, cytokines production were assessed to determine the degree of air way hyper responsiveness between animals pre-treated with Resiquimod and those which were untreated. Results: We show that, pre-treatment with Resiquimod before challenge with the allergen alleviates AHR in murine model. Through blocking experiments, we reveal that, the suppressive effect is dependent on induction of IL-27 and is associated with enhanced expression of immunomodulatory molecule B7-H1 (PD-L1) on pulmonary antigen presenting cells. In addition, Resiquimod application leads to inhibition of IL-17 which is reversed on blocking IL-27. Conclusions: Resiquimod driven alleviation AHR in murine models is dependent on IL-27 production and associated downstream mechanims such as induction of immunomodulatory molecules PD-L1 on antigen presenting cells. Concomitant Th2 to Th1 switching and, inhibition of Th17 through abolishment of IL-17 on Resiquimod application, leads to reduction in inflammatory responses usually associated with allergic airway hyper-responsiveness in this models. Thus, we believe targeting IL-27 dependent pathways in modulation of Th2 driven pathologies such as allergic asthma is a feasibly promising approach.