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Expression profiling of ileal mucosa in asthma reveals upregulation of innate immunity and genes characteristic of Paneth and goblet cells
Allergy, Asthma & Clinical Immunology ( IF 2.7 ) Pub Date : 2021-07-31 , DOI: 10.1186/s13223-021-00584-9
Jan K Nowak 1 , Marzena Dworacka 2 , Nazgul Gubaj 3 , Arystan Dossimov 3 , Zhumabek Dossimov 3 , Jarosław Walkowiak 1
Affiliation  

The expression profiles of the intestinal mucosa have not been comprehensively investigated in asthma. We aimed to explore this in the Correlated Expression and Disease Association Research (CEDAR) patient cohort. Differential expression analysis of ileal, transverse colon, and rectal biopsies were supplemented by a comparison of transcriptomes from platelets and leukocytes subsets, including CD4+, CD8+, CD14+, CD15+, and CD19+ cells. Asthma patients (n = 15) and controls (n = 15) had similar age (p = 0.967), body mass index (p = 0.870), similar numbers of females (80%) and smoking rates (13.3%). Significant differential expression was found in the ileum alone, and not in any other cell/tissue types. More genes were found to be overexpressed (1,150) than under-expressed (380). The most overexpressed genes included Fc Fragment of IgG Binding Protein (FCGBP, logFC = 3.01, pFDR = 0.015), Mucin 2 (MUC2, logFC = 2.78, pFDR = 0.015), and Alpha 1B Defensin (DEFA1B, logFC = 2.73, pFDR = 0.024). Gene ontology implicated the immune system, including interleukins 4 and 13, as well as antimicrobial peptides in this overexpression. There was concordance of gene over- (STAT1, XBP1) and underexpression (NELF, RARA) in asthma and Crohn’s disease ileum when our results were compared to another dataset (p = 3.66 × 10–7). Ileal mucosa in asthma exhibits a specific transcriptomic profile, which includes the overexpression of innate immune genes, mostly characteristic of Paneth and goblet cells, in addition to other changes that may resemble Crohn’s disease.

中文翻译:

哮喘回肠黏膜的表达谱揭示先天免疫的上调以及潘氏细胞和杯状细胞的基因特征

肠黏膜的表达谱在哮喘中尚未得到全面研究。我们旨在在相关表达和疾病关联研究 (CEDAR) 患者队列中探索这一点。回肠、横结肠和直肠活检的差异表达分析通过血小板和白细胞亚群(包括 CD4+、CD8+、CD14+、CD15+ 和 CD19+ 细胞)的转录组的比较进行补充。哮喘患者 (n = 15) 和对照组 (n = 15) 的年龄 (p = 0.967)、体重指数 (p = 0.870)、女性人数 (80%) 和吸烟率 (13.3%) 相似。仅在回肠中发现显着差异表达,在任何其他细胞/组织类型中均未发现。发现过度表达的基因(1,150)多于表达不足的基因(380)。过表达最多的基因包括 IgG 结合蛋白的 Fc 片段 (FCGBP, logFC = 3.01, pFDR = 0.015)、粘蛋白 2 (MUC2, logFC = 2.78, pFDR = 0.015) 和 Alpha 1B Defensin (DEFA1B, logFC, = 23)。 0.024)。基因本体论涉及免疫系统,包括白介素 4 和 13,以及这种过度表达中的抗菌肽。当我们的结果与另一个数据集进行比较时,哮喘和克罗恩病回肠中基因过度表达(STAT1、XBP1)和表达不足(NELF、RARA)存在一致性(p = 3.66 × 10-7)。哮喘中的回肠粘膜表现出特定的转录组学特征,其中包括先天免疫基因的过度表达,主要是潘氏细胞和杯状细胞的特征,以及可能类似于克罗恩病的其他变化。和 Alpha 1B 防御素(DEFA1B,logFC = 2.73,pFDR = 0.024)。基因本体论涉及免疫系统,包括白介素 4 和 13,以及这种过度表达中的抗菌肽。当我们的结果与另一个数据集进行比较时,哮喘和克罗恩病回肠中基因过度表达(STAT1、XBP1)和表达不足(NELF、RARA)存在一致性(p = 3.66 × 10-7)。哮喘中的回肠粘膜表现出特定的转录组学特征,其中包括先天免疫基因的过度表达,主要是潘氏细胞和杯状细胞的特征,以及可能类似于克罗恩病的其他变化。和 Alpha 1B 防御素(DEFA1B,logFC = 2.73,pFDR = 0.024)。基因本体论涉及免疫系统,包括白介素 4 和 13,以及这种过度表达中的抗菌肽。当我们的结果与另一个数据集进行比较时,哮喘和克罗恩病回肠中基因过度表达(STAT1、XBP1)和表达不足(NELF、RARA)存在一致性(p = 3.66 × 10-7)。哮喘中的回肠粘膜表现出特定的转录组学特征,其中包括先天免疫基因的过度表达,主要是潘氏细胞和杯状细胞的特征,以及可能类似于克罗恩病的其他变化。XBP1)和哮喘和克罗恩病回肠中的低表达(NELF,RARA),当我们的结果与另一个数据集进行比较时(p = 3.66 × 10-7)。哮喘中的回肠粘膜表现出特定的转录组学特征,其中包括先天免疫基因的过度表达,主要是潘氏细胞和杯状细胞的特征,以及可能类似于克罗恩病的其他变化。XBP1)和哮喘和克罗恩病回肠中的低表达(NELF,RARA),当我们的结果与另一个数据集进行比较时(p = 3.66 × 10-7)。哮喘中的回肠粘膜表现出特定的转录组学特征,其中包括先天免疫基因的过度表达,主要是潘氏细胞和杯状细胞的特征,以及可能类似于克罗恩病的其他变化。
更新日期:2021-08-01
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