Significance Conclusive identification of single genes contributing to complex autoimmune diseases has been challenging. Here, we positionally identify the vitamin D3 receptor gene ( Vdr ) as a driver of T cell-dependent inflammatory diseases using forward genetics. In the process, we generated congenic mice that overexpress Vdr in T cells as a consequence of natural polymorphisms in its promoter. These mice present a unique opportunity to study the immunomodulatory properties of VDR in a physiological setting. Moreover, the restricted overexpression of VDR to immune cells allows discrimination between immune-acting and confounding musculoskeletal effects of VDR. Our results suggest that VDR plays a role in T cell activation in parallel to the antiinflammatory actions mediated by its ligand.