Dataset Information

Reduced CD4+T Cell CXCR3 Expression in Patients With Allergic Rhinitis.

ABSTRACT: While T cells are considered to play a primary role in IgE-mediated atopic diseases, little is known about the systemic variations of T cell subsets from patients with allergic rhinitis (AR). To elucidate the characteristics of peripheral T cells, we analyzed natural killer, B cell, and T cell populations, performed T cell subset construction, and assessed chemokine receptor and associated serum cytokine expression in 25 AR patients and 20 healthy controls. Our results revealed increased levels of CD4+T cells, serum interleukin (IL)-10, IL-6, and interferon (IFN)-?, and reduced Th1 and Th17 subsets, identified by their chemokine receptors, in AR patients. These results suggest a systemic activation of T cell responses in AR. We further demonstrated that AR patients exhibit significantly reduced CD4+T cell CXCR3 expression, especially in patients with moderate-severe disease severity, demonstrating that CXCR3 is a potential key molecule that hinders the Th1/Th2 balance in AR pathology. Overall, systemic T cell activation occurred in AR patients and CXCR3 dramatically decreased in CD4+T cells, which may ultimately be used as a potential disease and/or therapeutic target.

SUBMITTER: Yu X

PROVIDER: S-EPMC7669911 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Reduced CD4<sup>+</sup>T Cell CXCR3 Expression in Patients With Allergic Rhinitis.

Yu Xiaofeng X Wang Meng M Cao Zhiwei Z

Frontiers in immunology 20201103

While T cells are considered to play a primary role in IgE-mediated atopic diseases, little is known about the systemic variations of T cell subsets from patients with allergic rhinitis (AR). To elucidate the characteristics of peripheral T cells, we analyzed natural killer, B cell, and T cell populations, performed T cell subset construction, and assessed chemokine receptor and associated serum cytokine expression in 25 AR patients and 20 healthy controls. Our results revealed increased levels ...[more]

PMID: 33224143

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Project description:BackgroundAllergic rhinitis (AR) is one of the most widespread immune conditions worldwide. However, common treatments often present with significant side effects or are cost-prohibitive for much of the population. A plethora of treatments have been used for the treatment of AR including antihistamines, steroids, and immune modulators. Among the treatments which have shown potential for efficacy in treating AR with a minimum of side effects but remains understudied is the conditionally essential amino acid taurine. Taurine has been previously shown to reduce AR symptoms. Here, we examine the role of taurine in modulating T regulatory cells, modulating the cytokine response in AR, and restoring healthy nasal mucosa.MethodsBlood samples from 20 healthy donors and 20 AR patients were compared for CD4+CD25+FoxP3+ T regulatory (Treg) cell population percentage, cytokine release, and STAT1 signaling with and without taurine treatment or IL-35 neutralization. An OVA-induced AR mouse model was administered vehicle, taurine, or taurine plus an IL-35 neutralizing antibody and assayed for sneezing frequency, inflammatory cytokine response, nasal mucosa goblet cell density, and T regulatory cell percentage. CD4+ cells were further examined for cytokine release, STAT1 phosphorylation, and response to an anti-IL-35 antibody with and without a STAT1 inhibitor.ResultsComparison of blood from normal donors and AR patients showed a reduction in CD4+CD25+FoxP3+ Treg cells in AR patients and a strong correlation between Treg percentage and IL-35 release. A similar pattern of Treg suppression was found in untreated AR mice when compared to normal control mice wherein there was a reduction in Treg percentage and a corresponding decrease in IL-35 release. AR mice also demonstrated increased sneezing frequency, an infiltration of goblet cell in nasal mucosa, and a reduction in IL-35 release from CD4+ cells. Conversely, IL-4, IL-5, and IL-13 secretion from CD4+ cells were increased in AR model mice, as was STAT1 phosphorylation. When AR mice were treated with taurine, sneezing frequency and nasal mucosa goblet cell content were reduced while Treg abundance was increased to that of normal mice. Accordingly, IL-35 release was restored, while IL-4, IL-5, and IL-13 secretion from CD4+ cells were suppressed. Likewise, STAT1 phosphorylation was inhibited with taurine treatment. Taurine-treated mice also given an IL-35 neutralizing antibody exhibited AR pathology including frequent sneezing and high nasal goblet cell content while retaining a restoration of Tregs. Furthermore, murine AR model CD4+ cells exposed to recombinant IL-35 responded with a reduction in inflammatory cytokine release and a decrease in STAT1 phosphorylation, mimicking the effect of taurine treatment.ConclusionsTaurine induces release of IL-35 in AR; IL-35 promotes the production of CD4+CD25+FoxP3+ Treg cells via a STAT1-dependent pathway. The restoration of Treg populations by taurine normalizes the inflammatory response, reduces AR symptomology, and reduces histopathologic signs of AR.

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

Reduced CD4+T Cell CXCR3 Expression in Patients With Allergic Rhinitis.

Publications

Reduced CD4<sup>+</sup>T Cell CXCR3 Expression in Patients With Allergic Rhinitis.

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