Abstract
Stimulator of interferon genes (STING) is a DNA sensor that responds to pathogens and induces type I interferon production. Herein, the role of STING in house dust mite extract (HDM)-induced allergic asthma was investigated. C57BL/6 wild-type (WT) and Sting−/− mice were intratracheally sensitized with HDM, and the bronchoalveolar lavage fluid (BALF), sera, lungs, and mediastinal lymph nodes (MLNs) were analyzed. The total and HDM-specific serum IgE levels were lower in Sting−/− mice than in WT mice. B cell and IgE-positive B cell proportion in BALF and MLNs, respectively, was significantly lower in Sting−/− mice than in WT mice. Additionally, cyclic GMP-AMP, a STING ligand, augmented total and HDM-specific serum IgE levels and B cell proportion in BALF when applied in combination with HDM. To elucidate the role of STING in IgE production, follicular helper T (Tfh) cells, which are involved in B cell maturation, were investigated. Tfh cell proportion in MLNs decreased in Sting−/− mice, and IL-4 and IL-13 production by HDM-restimulated MLN cells from HDM-sensitized mice was decreased in Sting−/− mice compared with WT mice. Thus, STING plays an important role in the maturation and class switching of IgE-producing B cells in allergic inflammation via Tfh cells.
Highlights
Stimulator of interferon genes (STING) is a DNA sensor that responds to pathogens and induces type I interferon production
The total and house dust mite extract (HDM)-specific serum IgE levels were lower in Sting−/− mice than WT mice
These results suggest that STING may affect T follicular helper (Tfh) cells and the class-switch recombination of B cells, resulting in defective IgE production
Summary
Stimulator of interferon genes (STING) is a DNA sensor that responds to pathogens and induces type I interferon production. The role of STING in house dust mite extract (HDM)-induced allergic asthma was investigated. Allergic asthma is a chronic inflammatory disease characterized by reversible airway obstruction, airway inflammation, and airway hypersensitivity This chronic inflammation is initiated by IgE cross-linking on mast cells and basophils, following the release of chemical mediators, such as histamine and leukotriene, causing airway smooth muscle contraction, airway hyperresponsiveness, and chronic eosinophil inflammation[16,17]. House dust extract mite (HDM), major cause of allergic asthma, activate signaling through Toll-like receptor (TLR) 4 and TLR2 and is involved in asthmatic inflammation[22,23,24,25]. We previously have reported that TLR9-mediated response to recognize single-stranded DNA exacerbates allergic asthma in a murine HDM-induced asthmatic model[31]. We attempted to clarify the involvement of STING in asthma using a Sting−/− HDMinduced asthmatic mouse model
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