Xiao-qing-long-tang ameliorates OVA-induced allergic rhinitis by inhibiting ILC2s through the IL-33/ST2 and JAK/STAT pathways

Phytomedicine. 2023 Oct:119:155012. doi: 10.1016/j.phymed.2023.155012. Epub 2023 Aug 6.

Abstract

Background: Allergic rhinitis (AR) is a chronic inflammatory disease of the nasal mucosa that is mediated by immunoglobulin E (IgE). Xiao-qing-long-tang (XQLT) is a traditional Chinese medicine compound that is widely used to treat respiratory diseases such as AR. However, the underlying mechanism of the effect of XQLT on AR remains unclear.

Purpose: To elucidate the effect of XQLT on ovalbumin (OVA)-induced AR and the mechanisms of action.

Methods: The therapeutic efficacy of XQLT was evaluated in a well-established OVA-induced AR mouse model. Nasal symptoms were analyzed, type 2 cytokines and OVA-sIgE levels were measured, nasal mucosa tissues were collected for histological analysis, and the changes of Group 2 innate lymphoid cells (ILC2s) and the IL-33/ST2 and JAK/STAT signaling pathways in the nasal mucosa were observed.

Results: XQLT significantly alleviated the nasal symptoms and histological damage to the nasal mucosa in AR mice, and reduced the levels of type 2 cytokines and OVA-sIgE. In addition, after XQLT treatment, the numbers of ILC2s in the nasal mucosa of AR mice were reduced, and the mRNA levels of the transcription factors GATA3 and ROR-α were decreased. Moreover, IL-33/ST2 signaling pathway was inhibited. The costimulatory cytokine associated JAK/STAT signaling pathway was also inhibited in ILC2s.

Conclusion: Our study demonstrated that XQLT regulated ILC2s through the IL-33/ST2 and JAK/STAT pathways to ameliorate type 2 inflammation in OVA-induced AR. These findings suggest that XQLT might be used to treat AR.

Keywords: Allergic rhinitis; IL-33/ST2 signaling; ILC2s; JAK/STAT pathway; Xiao-qing-long-tang.

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Disease Models, Animal
  • Immunity, Innate*
  • Interleukin-1 Receptor-Like 1 Protein / metabolism
  • Interleukin-33 / metabolism
  • Janus Kinases / metabolism
  • Lymphocytes
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin
  • Rhinitis, Allergic* / chemically induced
  • Rhinitis, Allergic* / drug therapy
  • STAT Transcription Factors / metabolism
  • Signal Transduction

Substances

  • Ovalbumin
  • sho-seiryu-to
  • Interleukin-1 Receptor-Like 1 Protein
  • Janus Kinases
  • Interleukin-33
  • STAT Transcription Factors
  • Cytokines