{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T23:21:47Z","timestamp":1794439307034,"version":"4.9.1"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T00:00:00Z","timestamp":1719792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Observational studies have indicated that immune dysregulation in primary sclerosing cholangitis (PSC) primarily involves intestinal-derived immune cells. However, the causal relationship between peripheral blood immune cells and PSC remains insufficiently understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A bidirectional two-sample Mendelian randomization (MR) analysis was implemented to determine the causal effect between PBC and 731 immune cells. All datasets were extracted from a publicly available genetic database. The standard inverse variance weighted (IVW) method was selected as the main method for the causality analysis. Cochran\u2019s <jats:italic>Q<\/jats:italic> statistics and MR-Egger intercept were performed to evaluate heterogeneity and pleiotropy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In forward MR analysis, the expression ratios of CD11c on CD62L+ myeloid DC (OR = 1.136, 95% CI = 1.032\u20131.250, <jats:italic>p<\/jats:italic> = 0.009) and CD62L-myeloid DC AC (OR = 1.267, 95% CI = 1.086\u20131.477, <jats:italic>p<\/jats:italic> = 0.003) were correlated with a higher risk of PSC. Each one standard deviation increase of CD28 on resting regulatory T cells (Treg) (OR = 0.724, 95% CI = 0.630\u20130.833, <jats:italic>p<\/jats:italic> &amp;lt; 0.001) and CD3 on secreting Treg (OR = 0.893, 95% CI = 0.823\u20130.969, <jats:italic>p<\/jats:italic> = 0.007) negatively associated with the risk of PSC. In reverse MR analysis, PSC was identified with a genetic causal effect on EM CD8+ T cell AC, CD8+ T cell AC, CD28\u2212 CD127\u2212 CD25++ CD8+ T cell AC, CD28\u2212 CD25++ CD8+ T cell AC, CD28\u2212 CD8+ T cell\/CD8+ T cell, CD28\u2212 CD8+ T cell AC, and CD45 RA\u2212 CD28\u2212 CD8+ T cell AC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study indicated the evidence of causal effects between PSC and immune cells, which may provide a potential foundation for future diagnosis and treatment of PSC.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1395513","type":"journal-article","created":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T04:51:57Z","timestamp":1719809517000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Causality of immune cells on primary sclerosing cholangitis: a bidirectional two-sample Mendelian randomization 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