Abstract
Autoimmune diseases (AIDs) result from intricate interactions among genetic, environmental and immune factors, with emerging evidence underscoring the role of the central nervous system (CNS) in their pathogenesis. In this study, we utilized two-sample Mendelian randomization to systematically explore the causal relationships between 3,935 brain imaging-derived phenotypes (IDPs) and eight AIDs, including atopic dermatitis, inflammatory bowel disease, lupus erythematosus, multiple sclerosis, myasthenia gravis, psoriasis, rheumatoid arthritis and type 1 diabetes. We identified nine IDPs with causal associations to eight representative AIDs. Mediation analysis uncovered eight potential immune cells or inflammatory factors bridging IDPs and AIDs. These findings provide compelling evidence for the CNS's involvement in autoimmune progresses through neuro-immune pathways and underscore potential diagnostic and therapeutic targets within the neuro-immune axis. This study introduces a novel framework for investigating interdisciplinary interventions that target CNS-immune interactions in the context of AIDs.