IL2‐inducible T‐cell kinase inhibitor ibrutinib reduces symptoms and Th2 differentiation in mouse allergic‐rhinitis model

• Published in: Drug development research 2022-04, Vol.83 (2), p.544-551
• Main Authors: Xu, Bing, Liu, Xiaozhe, Gao, Shihao
• Format: Article
• Language: English
• Subjects: Adenine - analogs & derivatives; Allergic rhinitis; Animals; Calcium signalling; Cell culture; Cell Differentiation; Cytokines; Cytokines - metabolism; Differentiation (biology); Disease Models, Animal; Enzyme inhibitors; Helper cells; House dust; Hypersensitivity; ibrutinib; Immune response; Immune system; Immunoglobulin E; Interleukin 2; ITK; Kinases; Lymphocytes; Lymphocytes T; Lymphoid tissue; Mice; Mice, Inbred BALB C; Myeloid cells; Nasal Mucosa - metabolism; NF-AT protein; Nuclear transport; Phosphorylation; Piperidines; Protein-Tyrosine Kinases; Rhinitis; Rhinitis - metabolism; Rhinitis, Allergic - drug therapy; Rhinitis, Allergic - metabolism; Signal transduction; Th2; Th2 Cells - cytology; Transcription factors; Translocation
• ISSN: 0272-4391; 1098-2299
• DOI: 10.1002/ddr.21884

Th2 and Th17 immune response contribute to allergic rhinitis (AR) development. Targeting Th2 and Th17 response has been shown to ameliorate AR. Ibrutinib is an inhibitor for IL2‐inducible T‐cell kinase, which can promote Th2 and Th17 immune response. We sought to investigate the effect of ibrutinib on AR and the underlying mechanisms. We established house dust mite‐induced AR mouse model and treated AR mice with ibrutinib. The symptoms of AR, serum level of immunoglobulin E, percentage of Th1, Th2, Th17, and Treg in nasal lymphoid tissues were monitored. We also established in vitro T cell differentiation cell culture model. The T cells were treated with ibrutinib and the expression of specific transcriptional factors and cytokines was measured. The activation of PLC‐γ1/calcium/NFAT2 signaling pathway was detected. Ibrutinib treatment had no effects on the development of lymphocytes and myeloid cells, but alleviated AR symptoms and decreased Th2 cell population in nasal lymphoid tissue. Meanwhile, iburitnib suppressed Th2 and Th17 differentiation in vitro. Moreover, iburitnib prevented phosphorylation of PLC‐γ1and nuclear translocation of NFAT2 in Th2 cells. Our results suggested that ibrutinib could ameliorate AR symptoms through suppression of Th2 differentiation in AR mouse model.