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

Sci Rep. 2021 Jun 23;11(1):13157. doi: 10.1038/s41598-021-92561-w.

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.

MeSH terms

  • Allergens / immunology*
  • Animals
  • Asthma / etiology
  • Asthma / genetics*
  • Asthma / immunology
  • B-Lymphocytes / immunology
  • Bronchoalveolar Lavage Fluid / cytology
  • Female
  • Immunoglobulin Class Switching
  • Immunoglobulin E / biosynthesis*
  • Immunoglobulin E / blood
  • Immunoglobulin E / immunology
  • Interleukin-13 / biosynthesis
  • Interleukin-13 / genetics
  • Interleukin-4 / biosynthesis
  • Interleukin-4 / genetics
  • Membrane Proteins / deficiency
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Nucleotides, Cyclic / pharmacology
  • Pyroglyphidae
  • Real-Time Polymerase Chain Reaction
  • T Follicular Helper Cells / immunology
  • Tissue Extracts / immunology*

Substances

  • Allergens
  • Interleukin-13
  • Membrane Proteins
  • Nucleotides, Cyclic
  • Sting1 protein, mouse
  • Tissue Extracts
  • cyclic guanosine monophosphate-adenosine monophosphate
  • Interleukin-4
  • Immunoglobulin E