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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders: Autoinflammatory Disorders
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1464479

Picolinate-mediated immunomodulation: Insights from mendelian randomization on the role of NK cell percentage in the pathogenesis of lichen planus

Provisionally accepted
Jianye Cao Jianye Cao 1Tiantao Du Tiantao Du 1*Jian Li Jian Li 2*Baiyu Chen Baiyu Chen 1*Xianting Xie Xianting Xie 1Guoshu Zhang Guoshu Zhang 1*Jia Feng Jia Feng 3*Tao Xu Tao Xu 4*
  • 1 The Clinical Medical College of Southwest Medical University, Luzhou, Sichuan Province, China
  • 2 Department of Thoracic surgery, Hejiang County People's Hospital, Luzhou, China
  • 3 Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, luzhou, China
  • 4 Department of Thoracic Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, China

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

    Background: Lichen planus (LP), an autoimmune disorder, remains incompletely understood in terms of its etiological mechanisms. This study aims to elucidate causal relationships among immune cell populations, plasma metabolites, and lichen planus using Mendelian randomization (MR) techniques.Methods: Employing a two-sample, two-step MR approach, with single nucleotide polymorphisms (SNP) serving as genetic instruments for both exposures and mediators, this study minimizes biases from confounding and reverse causality. Leveraging summary statistics from genome-wide association studies (GWAS) involving 731 immune cell traits (N = 3757), 1,400 plasma metabolite traits (N = 8299), and lichen planus (N = 367668), inverse variance weighting (IVW) is adopted as the primary MR analytical method. The total effect of immune cells traits on LP is decomposed into direct and indirect effects mediated by plasma metabolites.Results: MR analysis reveals causal associations for 28 immune cell traits and 38 plasma metabolites with LP (PIVW < 0.05). Specifically, NK % lymphocyte shows a negatively correlated causal effect with LP (ORIVW = 0.952; 95% CI: [0.910, 0.995], PIVW= 0.030). Among mediators, Picolinate significantly contributes, explaining 16.4% (95% CI: [28.3%, 4.54%]) of the association between NK % lymphocyte and LP.These findings support a potential protective causal effect of NK % lymphocyte on LP, partially mediated by Picolinate levels. Thus, interventions targeting Picolinate levels may mitigate LP burden attributed to low NK % lymphocyte counts. This study provides new evidence and insights into the pathogenesis of lichen planus, advancing our understanding of its underlying mechanisms.

    Keywords: immune cell, Lichen Planus, Mediation analysis, Mendelian randomization, Plasma metabolites

    Received: 14 Jul 2024; Accepted: 27 Nov 2024.

    Copyright: © 2024 Cao, Du, Li, Chen, Xie, Zhang, Feng and Xu. 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:
    Tiantao Du, The Clinical Medical College of Southwest Medical University, Luzhou, Sichuan Province, China
    Jian Li, Department of Thoracic surgery, Hejiang County People's Hospital, Luzhou, China
    Baiyu Chen, The Clinical Medical College of Southwest Medical University, Luzhou, Sichuan Province, China
    Guoshu Zhang, The Clinical Medical College of Southwest Medical University, Luzhou, Sichuan Province, China
    Jia Feng, Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, luzhou, China
    Tao Xu, Department of Thoracic Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan 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.