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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
Jinyin Xiao Jinyin Xiao 1,2Xiajun Guo Xiajun Guo 3*Keya Li Keya Li 1*Wenpeng Luo Wenpeng Luo 1Youwei Lin Youwei Lin 2Wenhong Lu Wenhong Lu 1*Zhenquan Wang Zhenquan Wang 1*
  • 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

The final, formatted version of the article will be published soon.

    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

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.