Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation

T(H)17 lymphocytes appear to be essential in the pathogenesis of numerous inflammatory diseases. We demonstrate here the expression of IL- 17 and IL- 22 receptors on blood- brain barrier endothelial cells (BBB-ECs) in multiple sclerosis lesions, and show that IL- 17 and IL- 22 disrupt BBB tight junctions in vitro and in vivo. Furthermore, T(H)17 lymphocytes transmigrate efficiently across BBB-ECs, highly express granzyme B, kill human neurons and promote central nervous system inflammation through CD4(+) lymphocyte recruitment.