2008 Brain Star Award Recipient - Hania Kebir
Recipient
Hania Kebir - Biosketch
PhD
Université de Montréal
Article
Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation. Hania Kebir, Katharina Kreymborg, Igal Ifergan, Aurore Dodelet-Devillers, Romain Cayrol, Monique Bernard, Fabrizio Giuliani, Nathalie Arbour, Burkhard Becher & Alexandre Prat. Nature Medicine. 2007 Oct, 13(10): 1173-5
Significance of the paper
The blood-brain barrier (BBB) plays a crucial role in protecting the central nervous system (CNS) by restricting entry of cells and molecules into the brain. In multiple sclerosis, breakdown of the BBB allows activated leukocytes to infiltrate the brain parenchyma, leading to the formation of the characteristic demyelinated lesions. The development of multiple sclerosis is known to be dependent on the presence in the CNS, of a population of myelin autoreactive T helper cells that express IL-17, therefore named TH17. While TH17 lymphocytes are required for the pathology of the disease, their function in humans had not yet been established.
In the present study, we show that through their interaction with BBB-endothelial cells, TH17 lymphocytes promote inflammation and infiltration of immune cells into the brain. We discovered that not only do TH17 cells efficiently cross the BBB, but they produce IL-17 and IL-22, cytokines that increase the permeability of the BBB by disrupting tight junction molecules between endothelial cells. Moreover, human TH17 cells promote lymphocyte recruitment across the BBB and induce neuronal damage. Hence our study further refines the phenotype of human TH17 lymphocytes and emphasizes the importance of TH17 lymphocyte infiltration into the CNS and their consequent involvement in lesion formation in multiple sclerosis.
Our findings have enhanced our current understanding of the initiation of immune responses in the CNS and have significantly contributed to the advancement of multiple sclerosis research in Canada. Moreover, they could open up new avenues for the development of therapeutic strategies for treatment of multiple sclerosis, which hopefully can benefit the 50,000 Canadians who suffer from this debilitating disease.