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TLR9-IL-2 axis exacerbates allergic asthma by preventing IL-17A hyperproduction.

ABSTRACT: Allergic asthma is one of most famous allergic diseases, which develops lung and airway inflammation. Recent studies have revealed the relationship between the pathology of allergic asthma and the increase of host-derived DNA in inflamed lung, but the role of the DNA-recognizing innate immune receptor for the inflammation is unknown well. Here we investigated the role of Toll-Like Receptor 9 in the pathogenesis of allergic asthma without synthesized CpG-ODNs. To examine that, we analyzed the pathology and immunology of house-dust-mite (HDM)-induced allergic asthma in Tlr9-/- mice and TLR9-inhibitory-antibody-treated mice. In Tlr9-/- mice, airway hyperresponsiveness (AHR) and the number of eosinophils decreased, and production of the Th2 cytokines IL-13, IL-5, and IL-4 was suppressed, compared with in wild-type mice. Interestingly, unlike Th2 cytokine production, IL-17A production was increased in Tlr9-/- mice. Furthermore, production of IL-2, which decreases IL-17A production, was reduced in Tlr9-/- mice. Blockade of TLR9 by treatment with TLR9-inhibitory-antibody, NaR9, effectively suppressed the development of allergic asthma pathology. IL-17A production in NaR9-treated mice was enhanced, which is comparable to Tlr9-/- mice. These results suggest that the TLR9-IL-2 axis plays an important role in Th2 inflammation by modulating IL-17A production in HDM-induced allergic asthma and that targeting of TLR9 might be a novel therapeutic method for allergic asthma.

SUBMITTER: Murakami Y 

PROVIDER: S-EPMC7581806 | BioStudies | 2020-01-01

REPOSITORIES: biostudies

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