Yao Wang, Ya-Kui Mou, Wan-Chen Liu, Han-Rui Wang, Xiao-Yu Song, Ting Yang, Chao Ren, Xi-Cheng Song
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We used a two-step MR approach to assess whether the causal effect was mediated by immune cells (n = 3,757).</p><p><strong>Results: </strong>Sterol ester and sphingomyelin played pathogenic roles in allergic asthma, AR, and allergic conjunctivitis; however, the effective subtypes differed. Among them, CD45RA- CD4+ mature T cells and CCR2 on CD14+ CD16+ monocytes affected the promoting impact of sterol ester's metabolism on allergic asthma and AR with different mediating proportions, while the role of sphingomyelin may not involve the immune cells. Moreover, we observed that HLA-DR on CD33- HLA DR+ myeloid cells, CD11b on CD66b++ myeloid cells, and IgD+ CD38- B cells played the most mediating effect of phosphatidylethanolamine (O-18:2_20:4) in allergic asthma, phosphatidylinositol (16:0_18:1) in AR, and phosphatidylethanolamine (18:0_18:2) in allergic conjunctivitis.</p><p><strong>Conclusion: </strong>This MR study provides evidence for specific lipid species associated with the risk of allergic diseases, especially sterol esters, and identifies the immune cells that mediate this causal relationship.</p>","PeriodicalId":13652,"journal":{"name":"International Archives of Allergy and Immunology","volume":" ","pages":"1-15"},"PeriodicalIF":2.5000,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Genetically Predicted Immune Cell-Mediated Effect of Lipid Metabolism on Allergic Diseases: A Two-Step, Mediation Mendelian Randomization Study.\",\"authors\":\"Yao Wang, Ya-Kui Mou, Wan-Chen Liu, Han-Rui Wang, Xiao-Yu Song, Ting Yang, Chao Ren, Xi-Cheng Song\",\"doi\":\"10.1159/000542036\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>An increasing number of studies have demonstrated that dynamic changes in lipid species can affect allergic diseases; however, the causal relationship and mediating role of immune cells remain unclear.</p><p><strong>Methods: </strong>We conducted a bidirectional two-sample mendelian randomization (MR) analysis using genome-wide association study (GWAS) data on 179 lipid species (n = 7,174) and three types of allergic diseases including allergic rhinitis (AR) (n = 370,158), allergic asthma (n = 219,753), and allergic conjunctivitis (n = 377,277). The principal model used was the inverse variance-weighted approach, and a series of sensitivity analyses were conducted to ensure the robustness of the results. We used a two-step MR approach to assess whether the causal effect was mediated by immune cells (n = 3,757).</p><p><strong>Results: </strong>Sterol ester and sphingomyelin played pathogenic roles in allergic asthma, AR, and allergic conjunctivitis; however, the effective subtypes differed. Among them, CD45RA- CD4+ mature T cells and CCR2 on CD14+ CD16+ monocytes affected the promoting impact of sterol ester's metabolism on allergic asthma and AR with different mediating proportions, while the role of sphingomyelin may not involve the immune cells. 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引用次数: 0
摘要
简介:越来越多的研究表明,脂质种类的动态变化会影响过敏性疾病;然而,其因果关系和免疫细胞的中介作用仍不清楚:越来越多的研究表明,脂质种类的动态变化会影响过敏性疾病;然而,免疫细胞的因果关系和中介作用仍不清楚:我们利用全基因组关联研究(GWAS)数据对179种脂质(n = 7 174)和三种过敏性疾病(包括过敏性鼻炎(AR)(n = 370 158)、过敏性哮喘(n = 219 753)和过敏性结膜炎(n = 377 277))进行了双向双样本泯灭随机化(MR)分析。使用的主要模型是反方差加权法,并进行了一系列敏感性分析,以确保结果的稳健性。我们采用两步MR法评估因果效应是否由免疫细胞介导(n = 3,757):结果:甾醇酯和鞘磷脂在过敏性哮喘、AR和过敏性结膜炎中起致病作用,但有效亚型不同。其中,CD45RA- CD4+ 成熟 T 细胞和 CD14+ CD16+ 单核细胞上的 CCR2 以不同的介导比例影响甾醇酯代谢对过敏性哮喘和 AR 的促进作用,而鞘磷脂的作用可能不涉及免疫细胞。此外,我们还观察到,CD33- HLA DR+髓系细胞上的 HLA-DR、CD66b++髓系细胞上的 CD11b 和 IgD+ CD38- B 细胞在过敏性哮喘中对磷脂酰乙醇胺(O-18:2_20:4)、在 AR 中对磷脂酰肌醇(16:0_18:1)、在过敏性结膜炎中对磷脂酰乙醇胺(18:0_18:2)的介导作用最大:这项磁共振研究提供了与过敏性疾病风险相关的特定脂质种类(尤其是甾醇酯)的证据,并确定了介导这种因果关系的免疫细胞。
Genetically Predicted Immune Cell-Mediated Effect of Lipid Metabolism on Allergic Diseases: A Two-Step, Mediation Mendelian Randomization Study.
Introduction: An increasing number of studies have demonstrated that dynamic changes in lipid species can affect allergic diseases; however, the causal relationship and mediating role of immune cells remain unclear.
Methods: We conducted a bidirectional two-sample mendelian randomization (MR) analysis using genome-wide association study (GWAS) data on 179 lipid species (n = 7,174) and three types of allergic diseases including allergic rhinitis (AR) (n = 370,158), allergic asthma (n = 219,753), and allergic conjunctivitis (n = 377,277). The principal model used was the inverse variance-weighted approach, and a series of sensitivity analyses were conducted to ensure the robustness of the results. We used a two-step MR approach to assess whether the causal effect was mediated by immune cells (n = 3,757).
Results: Sterol ester and sphingomyelin played pathogenic roles in allergic asthma, AR, and allergic conjunctivitis; however, the effective subtypes differed. Among them, CD45RA- CD4+ mature T cells and CCR2 on CD14+ CD16+ monocytes affected the promoting impact of sterol ester's metabolism on allergic asthma and AR with different mediating proportions, while the role of sphingomyelin may not involve the immune cells. Moreover, we observed that HLA-DR on CD33- HLA DR+ myeloid cells, CD11b on CD66b++ myeloid cells, and IgD+ CD38- B cells played the most mediating effect of phosphatidylethanolamine (O-18:2_20:4) in allergic asthma, phosphatidylinositol (16:0_18:1) in AR, and phosphatidylethanolamine (18:0_18:2) in allergic conjunctivitis.
Conclusion: This MR study provides evidence for specific lipid species associated with the risk of allergic diseases, especially sterol esters, and identifies the immune cells that mediate this causal relationship.
期刊介绍:
''International Archives of Allergy and Immunology'' provides a forum for basic and clinical research in modern molecular and cellular allergology and immunology. Appearing monthly, the journal publishes original work in the fields of allergy, immunopathology, immunogenetics, immunopharmacology, immunoendocrinology, tumor immunology, mucosal immunity, transplantation and immunology of infectious and connective tissue diseases.