BackgroundWe aimed to investigate the causal association betweenTIM-3, an immune checkpoint inhibitor, and anterior uveitis (AU), as well as associated systemic immune diseases.Materials and methodsWe performed two-sample Mendelian randomization (MR) analyses to estimate the causal effects ofTIM-3on AU and three associated systemic diseases, namely ankylosing spondylitis (AS), Crohn's disease (CD), and ulcerative colitis (UC). Single-nucleotide polymorphisms (SNPs) associated with AU, AS, CD, and UC were selected as the outcomes: AU GWAS with 2,752 patients with acute AU accompanied with AS (cases) and 3,836 AS patients (controls), AS GWAS with 968 cases and 336,191 controls, CD GWAS with 1,032 cases and 336,127 controls, and UC GWAS with 2,439 cases and 460,494 controls. TheTIM-3dataset was used as the exposure (n= 31,684). Four MR methods, namely, inverse-variance weighting (IVW), MR-Egger regression, weighted median, and weighted mode, were used in this study. Comprehensive sensitivity analyses were conducted to estimate the robustness of identified associations and the potential impact of horizontal pleiotropy.ResultsOur studies show thatTIM-3is significantly associated with CD using the IVW method (OR = 1.001, 95% CI = 1.0002–1.0018,P-value = 0.011). We also found thatTIM-3may be a protective factor for AU although these results lacked significance (OR = 0.889, 95% CI = 0.631–1.252,P-value = 0.5). No association was observed between the genetic predisposition to particularTIM-3and susceptibility to AS or UC in this study. No potential heterogeneities or directional pleiotropies were observed in our analyses.ConclusionAccording to our study, a small correlation was observed betweenTIM-3expression and CD susceptibility. Additional studies in different ethnic backgrounds will be necessary to further explore the potential roles and mechanisms of TIM-3 in CD.