Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation
Nature medicine, 2007•nature.com
TH17 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, TH17 lymphocytes
transmigrate efficiently across BBB-ECs, highly express granzyme B, kill human neurons
and promote central nervous system inflammation through CD4+ lymphocyte recruitment.
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, TH17 lymphocytes
transmigrate efficiently across BBB-ECs, highly express granzyme B, kill human neurons
and promote central nervous system inflammation through CD4+ lymphocyte recruitment.
Abstract
TH17 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, TH17 lymphocytes transmigrate efficiently across BBB-ECs, highly express granzyme B, kill human neurons and promote central nervous system inflammation through CD4+ lymphocyte recruitment.
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