Anti-Interleukin-9 Antibody Increases the Effect of Allergen-Specific Immunotherapy in Murine Allergic Rhinitis

Abstract

PurposeInterleukin (IL)-9 induces allergic responses; however, the roles of anti-IL-9 antibody in the induction of tolerance remain unclear. This study investigated the effects of anti-IL-9 antibody on oral tolerance (OT) in a mouse model of allergic rhinitis (AR).MethodsBALB/c mice were divided into 4 groups: the control, AR, OT, and OT with anti-IL-9 antibody (OT+IL9AB) groups. Ovalbumin (OVA) was used for sensitization and challenge. Mice in the OT and OT+IL9AB groups were fed OVA for immunotherapy. During immunotherapy, OT+IL9AB mice were injected with anti-IL-9 antibody. Allergic symptoms, tissue eosinophil counts, and serum OVA-specific immunoglobulin E (IgE) were measured. The mRNA expressions of cytokines and transcription factors of T cells of nasal mucosa were determined by real-time polymerase chain reaction (PCR). The protein levels of GATA3, ROR-γt, and Foxp3 in nasal mucosa were determined by Western blot. CD4+CD25+Foxp3+ T cells in the spleen were analyzed by flow cytometry.ResultsAdministration of anti-IL-9 antibody decreased allergic symptoms, OVA-specific IgE levels, and eosinophil counts. In addition, it inhibited T-helper (Th) 2 responses, but had no effect on Th1 responses. Protein levels of ROR-γt and mRNA levels of PU.1 and ROR-γt were reduced by anti-IL-9 antibody. Anti-IL-9 antibody increased Foxp3 and IL-10 mRNA expression, Foxp3 protein, and induction of CD4+CD25+Foxp3+ T cells.ConclusionsAnti-IL-9 antibody decreased allergic inflammation through suppression of Th2 and Th17 cells. Anti-IL-9 antibody enhanced the tolerogenic effects of regulatory T cells. These results suggest that anti-IL-9 antibody might represent a potential therapeutic agent for allergen immunotherapy in patients with uncontrolled allergic airway disease.

Involvement of T-Helper 9 Activation in a Mouse Model of Allergic Rhinitis

“…These results indicate that the expression of eosinophils invasion is closely related to IL-9 expression. Our results further confirm that IL-9 is closely related to the AR model, and IL-9 silencing can improve the symptoms of AR [ 22 ]. Although TH1 and TH2 are both CD4+ helper cells, their function is based on the secretion of cytokines IFN-γ and IL-4 [ 22 ].…”

“…The number of IL-9-positive cells in nasal mucosa was correlated with the number of eosinophils in nasal mucosa, and about 1/3 of the cells were T cells. After 2 years of immunotherapy, the levels of IL-9 protein and mRNA were significantly decreased in AR patients [ 22 ]. These results suggest that TH9 cells secrete IL-9, which likely contributes to AR pathogenesis.…”

Sustained Inhibition of the IL4/IL13 Receptor Complex during Allergen Specific Immunotherapy

“…Another unexpected observation was that AIT alone or in combination with IL-4 Mutein could significantly decrease the abundance of Rorγt + cells among the CD4 + subset. This observation that was also made by other groups (Shin et al, 2017) illustrates that AIT does not only affect TH2 and regulatory T cells but has various effects on different cell types. At this time point the previously reduced total and OVA-specific IgE levels in the IL-4 Mutein-and AIT-treated mice had increased to the level of the positive control mice.…”

Acupoint application inhibits nerve growth factor and attenuates allergic inflammation in allergic rhinitis model rats

“…An increased incidence of allergic rhinitis (AR) has been manifested worldwide in recent years [1,2]. AR, a chronic inflammatory disease of nasal mucosa, is mediated by immunoglobulin E (IgE) in T helper (TH) 2 type [3,4].…”