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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders: Autoinflammatory Disorders
Volume 15 - 2024 |
doi: 10.3389/fimmu.2024.1416562
This article is part of the Research Topic Lipid-Immune Interplay in Chronic Inflammatory-Based Disorders View all 3 articles
Role of myeloid cells in mediating the effects of lipids on ulcerative colitis
Provisionally accepted- 1 The Second Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha, Anhui Province, China
- 2 Hunan University of Chinese Medicine, Changsha, China
- 3 The First People's Hospital of Xiangtan City, Xiangtan, Hunan Province, China
Objective: To evaluate the causal relationship between lipids and ulcerative colitis (UC) through Mendelian Randomization (MR), and to further investigate the involvement of immune cells in mediating this process. Methods: Utilizing summary statistics from genome-wide association studies (GWAS) of individuals with European ancestry, we analyzed the causal link between 179 lipid types and UC (2,569 UC cases and 453,779 controls) through Two-sample Mendelian randomization (2SMR) and Bayesian-weighted MR (BWMR). Based on this, a mediation screening of 731 immune cell phenotypes was conducted to identify exposure and mediator factors. Lastly, the role and proportion of immune cells in mediating the causal effects of lipids on UC were assessed via reverse MR (RMR) and two-step MR. Results: The results of MR showed that there was a causal relationship between the six genetically predicted lipid types and UC (P <0.05), and the four immune cell phenotypes were identified as mediators of the association between lipids and UC. Notably, Phosphatidylcholine (PC) (16:0_0:0) served as the exposure factor, and myeloid cells CD11b on CD33+ HLA DR+ CD14dim acted as the mediator. Mediation analysis showed that CD11b on CD33+ HLA DR+ CD14dim had a mediation effect of -0.0205 between PC (16:0_0:0) and UC, with the mediation effect ratio at 15.38%. Conclusion: Our findings elucidate the causal effect of lipids on UC and identify the significant mediating role of myeloid cells CD11b on CD33+ HLA DR+ CD14dim in regulating UC through PC (16:0_0:0), offering new pathways and strategies for UC clinical treatment.
Keywords: Mendelian randomization, Lipids, Phosphatidylcholine, immune cells, Myeloid Cells, ulcerative colitis
Received: 12 Apr 2024; Accepted: 15 Aug 2024.
Copyright: © 2024 Xiao, Guo, Li, Luo, Lin, Lu and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Xiajun Guo, The First People's Hospital of Xiangtan City, Xiangtan, Hunan Province, China
Keya Li, The Second Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha, Anhui Province, China
Wenhong Lu, The Second Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha, Anhui Province, China
Zhenquan Wang, The Second Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha, Anhui Province, China
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