A retrospective review of colonic samples from 20 patients receiving TAC monotherapy identified no necrosis but neutrophilic cryptitis (60%), apoptotic crypt cells (55%), and crypt destruction (35%), and more than half of these patients had endoscopic colitis, reflecting possible drug-induced immune dysregulation.12 Notably, CNIs can also cause arterial endothelial impairment, disrupting the balance between vasodilators and vasoconstrictors, and promoting vascular inflammation via toll-like receptor-4 signaling, as seen in TAC-associated cerebral vasoconstriction syndrome.13–15. This evidence concerns the gene TLR4 and persistent truncus arteriosus.