Dataset Information

The role of TRPV1 in the CD4+ T cell-mediated inflammatory response of allergic rhinitis.

ABSTRACT: Transient receptor potential vanilloid 1 (TRPV1), which has been identified as a molecular target for the activation of sensory neurons by various painful stimuli, was reported to regulate the signaling and activation of CD4+ T cells. However, the role of TRPV1 in CD4+ T cell in allergic rhinitis remains poorly understood. In this study, TRPV1 expression was localized in CD4+ T cells. Both knockout and chemical inhibition of TRPV1 suppressed Th2/Th17 cytokine production in CD4 T cells and Jurkat T cells, respectively, and can suppress T cell receptor signaling pathways including NF-κB, MAP kinase, and NFAT. In TRPV1 knockout allergic rhinitis (AR) mice, eosinophil infiltration, Th2/Th17 cytokines in the nasal mucosa, and total and ova-specific IgE levels in serum decreased, compared with wild-type AR mice. The TRPV1 antagonists, BCTC or theobromine, showed similar inhibitory immunologic effects on AR mice models. In addition, the number of TRPV1+/CD4+ inflammatory cells increased in the nasal mucosa of patients with AR, compared with that of control subjects. Thus, TRPV1 activation on CD4+ T cells is involved in T cell receptor signaling, and it could be a novel therapeutic target in AR.

SUBMITTER: Samivel R

PROVIDER: S-EPMC4807989 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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The role of TRPV1 in the CD4+ T cell-mediated inflammatory response of allergic rhinitis.

Samivel Ramachandran R Kim Dae Woo DW Son Hye Ran HR Rhee Yun-Hee YH Kim Eun Hee EH Kim Ji Hye JH Bae Jun-Sang JS Chung Young-Jun YJ Chung Phil-Sang PS Raz Eyal E Mo Ji-Hun JH

Oncotarget 20160101 1

Transient receptor potential vanilloid 1 (TRPV1), which has been identified as a molecular target for the activation of sensory neurons by various painful stimuli, was reported to regulate the signaling and activation of CD4+ T cells. However, the role of TRPV1 in CD4+ T cell in allergic rhinitis remains poorly understood. In this study, TRPV1 expression was localized in CD4+ T cells. Both knockout and chemical inhibition of TRPV1 suppressed Th2/Th17 cytokine production in CD4 T cells and Jurkat ...[more]

PMID: 26700618

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Project description:BackgroundRhinitis is a complex condition characterized by various subtypes, including allergic rhinitis (AR), which involves inflammatory reactions. The objective of this research was to identify crucial genes associated with inflammatory response that are relevant for the treatment and diagnosis of AR.MethodsWe acquired the AR-related expression datasets (GSE75011 and GSE50223) from the Gene Expression Omnibus (GEO) database. In GSE75011, we compared the gene expression profiles between the HC and AR groups and identified differentially expressed genes (DEGs). By intersecting these DEGs with inflammatory response-related genes (IRGGs), resulting in the identification of differentially expressed inflammatory response-related genes (DIRRGs). Afterwards, we utilized the protein-protein interaction (PPI) network, machine learning algorithms, namely least absolute shrinkage and selection operator (LASSO) regression and random forest, to identify the signature markers. We employed a nomogram to evaluate the diagnostic effectiveness of the method, which has been confirmed through validation using GSE50223. qRT-PCR was used to confirm the expression of diagnostic genes in clinical samples. In addition, a consensus clustering method was employed to categorize patients with AR. Subsequently, extensive investigation was conducted to explore the discrepancies in gene expression, enriched functions and pathways, as well as potential therapeutic drugs among these distinct subtypes.ResultsA total of 22 DIRRGs were acquired, which participated in pathways including chemokine and TNF signaling pathway. Additionally, machine learning algorithms identified NFKBIA, HIF1A, MYC, and CCRL2 as signature genes associated with AR's inflammatory response, indicating their potential as AR biomarkers. The nomogram based on feature genes could offer clinical benefits to AR patients. We discovered two molecular subtypes, C1 and C2, and observed that the C2 subtype exhibited activation of immune- and inflammation-related pathways.ConclusionsNFKBIA, HIF1A, MYC, and CCRL2 are the key genes involved in the inflammatory response and have the strongest association with the advancement of disease in AR. The proposed molecular subgroups could provide fresh insights for personalized treatment of AR.

Dataset Information

The role of TRPV1 in the CD4+ T cell-mediated inflammatory response of allergic rhinitis.

Publications

The role of TRPV1 in the CD4+ T cell-mediated inflammatory response of allergic rhinitis.

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