Platelet perturbation to ciprofloxacin exacerbates IBD through regulation of HLA DR on CD14⁻CD16⁺ monocytes.

Inflammatory bowel disease (IBD) is a chronic and relapsing disorder influenced by immune dysfunction and other systemic factors. However, the exact pathogenesis of IBD remains incompletely understood. In addition to the traditionally recognized immune dysregulation, recent studies have suggested that the hematopoietic system also plays an important role in the development and progression of IBD. In this study, we applied mediation Mendelian randomization analysis to systematically investigate the role of blood cell perturbation phenotypes and immune cells in IBD pathogenesis. A total of 91 human blood cell perturbation phenotypes were used as exposures, IBD cases from Finnish and European populations served as outcomes, and 731 immune cell phenotypes were assessed as potential mediators. Our results revealed that HLA-DR expression on CD14⁻CD16⁺ monocytes exerts a protective effect by reducing the risk of IBD. However, platelet disturbance in response to ciprofloxacin downregulates HLA-DR expression on these monocytes, thereby weakening this protective effect and increasing disease risk. In conclusion, this study systematically explores a potential mechanism by which platelet perturbation contributes to the development and progression of IBD through immune cell mediation, using mediation Mendelian randomization.