Crucial role of stimulator of interferon genes-dependent signaling in house dust mite extract-induced IgE production

• Published in: Scientific Reports Vol. 11; no. 1; pp. 13157 - 11
• Main Authors: Nunokawa, Hiroki, Murakami, Yusuke, Ishii, Takashi, Narita, Tomoya, Ishii, Haruyuki, Takizawa, Hajime, Yamashita, Naomi
• Format: Journal Article
• Language: English
• Published: London Springer Science and Business Media LLC 23.06.2021; Nature Publishing Group UK; Nature Publishing Group; Nature Portfolio
• Subjects: 631/250; 631/80; 692/699; Airway management; Allergens; Allergies; AMP; Animals; Asthma; B-Lymphocytes; Bronchoalveolar Lavage Fluid; Bronchus; Class switching; Cyclic GMP; Experiments; Female; Flow cytometry; House dust; Humanities and Social Sciences; Hypersensitivity; Immunoglobulin Class Switching; Immunoglobulin E; Inflammation; Interferon; Interleukin 13; Interleukin 4; Lavage; Ligands; Lymph nodes; Lymphatic system; Lymphocytes B; Medicine; Membrane Proteins; Mice; Mice, Inbred C57BL; Mites; multidisciplinary; Neutrophils; Nucleotides, Cyclic; Pharmaceutical sciences; Pyroglyphidae; Q; R; Real-Time Polymerase Chain Reaction; Rodents; Science; Science (multidisciplinary); Signal transduction; T Follicular Helper Cells; Tissue Extracts
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-92561-w

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.