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Undersized telomeres in regulatory T cells link to the pathogenesis of allergic rhinitis.

ABSTRACT: Telomeres are an important biomarker in the cell destiny. The relationship between telomeres and regulatory T cells (Tregs) has not yet been investigated. The objective of this study is to evaluate the link between Tregs' telomere length and allergic rhinitis (AR)'s pathogenesis. Here, we report that low telomerase activity and high endoplasmic reticulum stress status were observed in Tregs from AR patients, as shown in the results. Immune regulatory molecules levels were correlated with the length of Tregs' telomeres. The immune-suppressive functions of Tregs were associated with the telomere length/Telomerase reverse transcriptase/Telomerase protein component 1 status in Tregs. The levels of telomere length/telomerase in airway Tregs were reduced by sensitization. Endoplasmic reticulum stress signaling pathway of proline-rich receptor-like protein kinase-eukaryotic translation initiation factor 2A (eIF2a) was associated with the regulation of telomerase. Inhibiting eIF2a had an effect on upregulating telomerase activity in Tregs and mitigating experimental AR.

SUBMITTER: Xue J

PROVIDER: S-EPMC10777067 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Undersized telomeres in regulatory T cells link to the pathogenesis of allergic rhinitis.

Xue Jinmei J Liu Zhizhen Z Liao Yun Y Zhang Xiwen X Liu Yu Y Mo Lihua L Dong Rui R Li Qiang Q Sun Xizhuo X Xie Jun J Yang Pingchang P

iScience 20231210 1

Telomeres are an important biomarker in the cell destiny. The relationship between telomeres and regulatory T cells (Tregs) has not yet been investigated. The objective of this study is to evaluate the link between Tregs' telomere length and allergic rhinitis (AR)'s pathogenesis. Here, we report that low telomerase activity and high endoplasmic reticulum stress status were observed in Tregs from AR patients, as shown in the results. Immune regulatory molecules levels were correlated with the len ...[more]

PMID: 38205251

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Project description:BackgroundAllergic rhinitis (AR) and chronic spontaneous urticaria (CSU) are often concurrent in patients. Changes in DNA methylation affect T cell biological processes, which may explain the occurrence and progression of comorbidity. However, downstream regulatory pathways of DNA methylation in two diseases and the underlying mechanisms have not been fully elucidated.MethodsThe GSE50101, GSE72541, GSE50222 and OEP002482 were mined for the identification of differentially expressed genes (DEGs) or co-expressed genes and differentially methylated genes (DMGs) in AR and CSU patients. We applied GO analysis and consensus clustering to study the potential functions and signal pathways of selected genes in two diseases. GSVA and logistic regression analysis were used to find the regulatory pathway between DNA methylation and activation patterns of CD4+ T cells. Besides, we used the Illumina 850k chip to detect DNA methylation expression profiles and recognize the differentially methylated CpG positions (DMPs) on corresponding genes. Finally, we annotated the biological process of these genes using GO and KEGG pathway analysis.ResultThe AR-related DEGs were found closely related to the differentiation and activation of CD4+ T cells. The DEGs or co-expressed genes of CD4+ T cells in AR and CSU patients were also clustered using GO and KEGG analysis and we got 57 co-regulatory pathways. Furthermore, logistic regression analysis showed that the regulation of cellular component size was closely related to the activation of CD4+ T cells regulated by DNA methylation. We got self-tested data using the Illumina 850k chip and identified 98 CpGs that were differentially methylated in patients. Finally, we mapped the DMPs to 15 genes and found that they were mainly enriched in the same CD4+T cell regulating pathway.ConclusionOur study indicated that DNA methylation affected by pollen participated in the activation patterns of CD4 + T cells, providing a novel direction for the symptomatic treatment of the co-occurrence of AR and CSU.

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.

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Undersized telomeres in regulatory T cells link to the pathogenesis of allergic rhinitis.

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Undersized telomeres in regulatory T cells link to the pathogenesis of allergic rhinitis.

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