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Murine allergic rhinitis and nasal Th2 activation are mediated via TSLP- and IL-33-signaling pathways.

ABSTRACT: Thymic stromal lymphopoietin (TSLP) and IL-33 are epithelium-derived proallergic cytokines that contribute to allergic diseases. Although the involvement of TSLP in allergic rhinitis (AR) is suggested, the exact role of TSLP in AR is poorly understood. Furthermore, the relative contribution of TSLP and IL-33 in nasal allergic responses has not been described. In this study, we examined the roles of TSLP and IL-33 in AR by analyzing acute and chronic AR models. Acute AR mice were intraperitoneally immunized with ragweed, then intranasally challenged with ragweed pollen for four consecutive days. Chronic AR mice were nasally administrated ragweed pollen on consecutive days for 3 weeks. In both models, TSLP receptor (TSLPR)-deficient mice showed defective sneezing responses and reduced serum ragweed-specific IgE levels compared with wild-type (WT) mice. Analyses of bone-marrow chimeric mice demonstrated that hematopoietic cells were responsible for defective sneezing in TSLPR-deficient mice. In addition, Fc?RI(+)-cell-specific TSLPR-deficient mice showed partial but significant reduction in sneezing responses. Of note, Th2 activation and nasal eosinophilia were comparable between WT and TSLPR-deficient mice. ST2- and IL-33-deficient mice showed defective Th2 activation and nasal eosinophilia to acute, but not chronic, ragweed exposure. TSLPR and ST2 double-deficient mice showed defective Th2 activation and nasal eosinophilia even after chronic ragweed exposure. These results demonstrate that TSLPR signaling is critical for the early phase response of AR by controlling the IgE-mast-cell/basophil pathway. The IL-33/ST2 pathway is central to nasal Th2 activation during acute allergen exposure, but both TSLPR and ST2 contribute to Th2 responses in chronically allergen-exposed mice.

SUBMITTER: Akasaki S

PROVIDER: S-EPMC4885219 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Murine allergic rhinitis and nasal Th2 activation are mediated via TSLP- and IL-33-signaling pathways.

Akasaki Shoko S Matsushita Kazufumi K Kato Yukinori Y Fukuoka Ayumi A Iwasaki Naruhito N Nakahira Masakiyo M Fujieda Shigeharu S Yasuda Koubun K Yoshimoto Tomohiro T

International immunology 20151001 2

Thymic stromal lymphopoietin (TSLP) and IL-33 are epithelium-derived proallergic cytokines that contribute to allergic diseases. Although the involvement of TSLP in allergic rhinitis (AR) is suggested, the exact role of TSLP in AR is poorly understood. Furthermore, the relative contribution of TSLP and IL-33 in nasal allergic responses has not been described. In this study, we examined the roles of TSLP and IL-33 in AR by analyzing acute and chronic AR models. Acute AR mice were intraperitoneall ...[more]

PMID: 26428949

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Project description:IntroductionAlthough recent studies have shown that the human microbiome is involved in the pathogenesis of allergic diseases, the impact of microbiota on allergic rhinitis (AR) and non-allergic rhinitis (nAR) has not been elucidated. The aim of this study was to investigate the differences in the composition of the nasal flora in patients with AR and nAR and their role in the pathogenesis.MethodFrom February to September 2022, 35 AR patients and 35 nAR patients admitted to Harbin Medical University's Second Affiliated Hospital, as well as 20 healthy subjects who underwent physical examination during the same period, were subjected to 16SrDNA and metagenomic sequencing of nasal flora.ResultsThe microbiota composition of the three groups of study subjects differs significantly. The relative abundance of Vibrio vulnificus and Acinetobacter baumanni in the nasal cavity of AR patients was significantly higher when compared to nAR patients, while the relative abundance of Lactobacillus murinus, Lactobacillus iners, Proteobacteria, Pseudomonadales, and Escherichia coli was lower. In addition, Lactobacillus murinus and Lacttobacillus kunkeei were also negatively correlated with IgE, while Lacttobacillus kunkeei was positively correlated with age. The relative distribution of Faecalibacterium was higher in moderate than in severe AR patients. According to KEGG functional enrichment annotation, ICMT(protein-S-isoprenylcysteine O-methyltransferase,ICMT) is an AR microbiota-specific enzyme that plays a role, while glycan biosynthesis and metabolism are more active in AR microbiota. For AR, the model containing Parabacteroides goldstemii, Sutterella-SP-6FBBBBH3, Pseudoalteromonas luteoviolacea, Lachnospiraceae bacterium-615, and Bacteroides coprocola had the highest the area under the curve (AUC), which was 0.9733(95%CI:0.926-1.000) in the constructed random forest prediction model. The largest AUC for nAR is 0.984(95%CI:0.949-1.000) for the model containing Pseudomonas-SP-LTJR-52, Lachnospiraceae bacterium-615, Prevotella corporis, Anaerococcus vaginalis, and Roseburia inulinivorans.ConclusionIn conclusion, patients with AR and nAR had significantly different microbiota profiles compared to healthy controls. The results suggest that the nasal microbiota may play a key role in the pathogenesis and symptoms of AR and nAR, providing us with new ideas for the treatment of AR and nAR.

Dataset Information

Murine allergic rhinitis and nasal Th2 activation are mediated via TSLP- and IL-33-signaling pathways.

Publications

Murine allergic rhinitis and nasal Th2 activation are mediated via TSLP- and IL-33-signaling pathways.

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