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

H Kebir, K Kreymborg, I Ifergan, A Dodelet-Devillers… - Nature medicine, 2007 - nature.com
H Kebir, K Kreymborg, I Ifergan, A Dodelet-Devillers, R Cayrol, M Bernard, F Giuliani
Nature medicine, 2007nature.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.
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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