Abstract
Dendritic cells (DCs) play critical roles in atopic diseases, orchestrating both innate and adaptive immune systems. Nevertheless, limited information is available regarding the mechanism through which DCs induce hyperresponsiveness in patients with allergies. This study aims to reveal novel genetic alterations and future therapeutic target molecules in the DCs from patients with allergies using whole transcriptome sequencing. Transcriptome sequencing of human BDCA-3+/CD11c+ DCs sorted from peripheral blood monocytes obtained from six patients with allergies and four healthy controls was conducted. Gene expression profile data were analyzed, and an ingenuity pathway analysis was performed. A total of 1638 differentially expressed genes were identified at p-values < 0.05, with 11 genes showing a log2-fold change ≥1.5. The top gene network was associated with cell death/survival and organismal injury/abnormality. In validation experiments, amphiregulin (AREG) showed consistent results with transcriptome sequencing data, with increased mRNA expression in THP-1-derived DCs after Der p 1 stimulation and higher protein expression in myeloid DCs obtained from patients with allergies. This study suggests an alteration in the expression of DCs in patients with allergies, proposing related altered functions and intracellular mechanisms. Notably, AREG might play a crucial role in DCs by inducing the Th2 immune response.
Highlights
In atopic diseases, such as asthma and allergic rhinitis, CD4+ Th2-driven immune responses play a crucial role [1]
The differentiation of naïve T cells into Th1/Th17 cells is related to cell-mediated immunity, which is dominant in autoimmune inflammatory diseases, whereas Th2-skewed immune imbalance leads to the dysregulation of antibody-mediated immunity in allergic diseases, including asthma, atopic dermatitis, and allergic rhinitis [9,10,11]
Among the selected Differentially Expressed Genes (DEGs), AREG was validated through experiments in THP-1-derived Dendritic cells (DCs) stimulated with an allergen and western blot analysis in DCs extracted from allergy patients
Summary
In atopic diseases, such as asthma and allergic rhinitis, CD4+ Th2-driven immune responses play a crucial role [1]. Dendritic cells (DCs) are important antigen-presenting cells that initiate allergic inflammation by orchestrating both the innate and adaptive immune systems [2,3]. The differentiation of naïve T cells into Th1/Th17 cells is related to cell-mediated immunity, which is dominant in autoimmune inflammatory diseases, whereas Th2-skewed immune imbalance leads to the dysregulation of antibody-mediated immunity in allergic diseases, including asthma, atopic dermatitis, and allergic rhinitis [9,10,11]. Th2-mediated induction of naïve T cells has not been extensively investigated, and functional genomes or their interactions in DCs that lead to Th2-driven immune responses remain unknown
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