DHH and multiple sclerosis: Here, we demonstrated for the first time that DHH is down-regulated at the BBB during EAE and that DHH knockdown is sufficient to induce BBB permeability by inhibiting CDH5 and CLDN5 expression through the modulation of FOXO1 activity, strengthening the idea that HH signaling is essential to control BBB integrity both physiologically and under multiple sclerosis conditions.