Bimin Kang ameliorates the minimal persistent inflammation in allergic rhinitis by reducing BCL11B expression and regulating ILC2 plasticity

Abstract

Ethnopharmacological relevanceMinimal persistent inflammation (MPI) is a major contributor to the recurrence of allergic rhinitis (AR). The traditional Chinese herbal medicine known as Bimin Kang Mixture (BMK) have been used in clinics for decades to treat AR, which can relieve AR symptoms, reduce inflammatory response and improve immune function. However, its mechanism in controlling MPI is still unclear. Aim of the studyThis study aims to assess the therapeutic effect of BMK on MPI, and elaborate the mechanism involved in BMK intervention in BCL11B regulation of type 2 innate lymphoid cell (ILC2) plasticity in the treatment of MPI. Material and methodsThe effect of BMK (9.1 ml/kg) and Loratadine (15.15 mg/kg) on MPI was evaluated based on symptoms, pathological staining, and ELISA assays. RT-qPCR and flow cytometry were also employed to assess the expression of BCL11B, IL-12/IL-12Rβ2, and IL-18/IL-18Rα signaling pathways associated with ILC2 plasticity in the airway tissues of MPI mice following BMK intervention. ResultsBMK restored the airway epithelial barrier, and markedly reduced inflammatory cells (eosinophils, neutrophils) infiltration (P < 0.01) and goblet cells hyperplasia (P < 0.05). BCL11B expression positively correlated with the ILC2 proportion in the lungs and nasal mucosa of AR and MPI mice (P < 0.01). BMK downregulated BCL11B expression (P < 0.05) and reduced the proportion of ILC2, ILC3 and ILC3-like ILC2 subsets (P < 0.05). Moreover, BMK promoted the conversion of ILC2 into an ILC1-like phenotype through IL-12/IL-12Rβ2 and IL-18/IL-18Rα signaling pathways in MPI mice. ConclusionBy downregulating BCL11B expression, BMK regulates ILC2 plasticity and decreases the proportion of ILC2, ILC3, and ILC3-like ILC2 subsets, promoting the conversion of ILC2 to ILC1, thus restoring balance of ILC subsets in airway tissues and control MPI.