News #ECTRIMS2016 – Protein Seen as New Target in Preventing Brain Inflammation in MS #ECTRIMS2016 – Protein Seen as New Target in Preventing Brain Inflammation in MS by Patricia Inacio, PhD | September 16, 2016 Share this article: Share article via email Copy article link Researchers found that blocking a protein,Ā known asĀ integrin alpha 8, may workĀ to prevent inflammation in the central nervous system of patients with multiple sclerosis (MS). The results were revealedĀ in an oral presentation, āIntegrin alpha8 is a novel mediator of T lymphocyte migration across the CNS barriers,ā atĀ theĀ 32nd Congress of theĀ European Committee for Treatment and Research in Multiple SclerosisĀ (ECTRIMS), taking placeĀ in London on Sept. 14ā17. A critical component of MS pathogenesis is the migration of inflammatory immune cells (such as T-cells) from the blood intoĀ the central nervous system (CNS). The CNS tries to prevent such harmful migration through two important and tightly regulated barriers: theĀ blood-brain barrier (BBB) and the blood-meningeal barrier (BMB). A key protein mediating the migration of immune cells, called lymphocytes, from the peripheral blood circulation and across the CNS barriers is integrin beta1. The protein’s role in this migration, in fact, can be seen in the strong clinical efficacy of Tysabri (natalizumab), a monoclonal antibody that targets integrin alpha4beta1. (AĀ downside of Tysabri treatment, however, is that it also targets integrin alpha4beta1 in other tissues, impairing the standard surveillance work of ourĀ immune systems.Ā This can lead to an increased susceptibility to severe viral infections.) Researchers aimed to find newĀ beta1 integrin partners involved in the migration of detrimental lymphocytes across the CNS vasculature. TheyĀ found that a specific subset of T lymphocytes, the pro-inflammatory TH17 cells, express integrin alpha8, and that this protein interacts specifically with integrin beta1. The team also foundĀ that the expression of integrin alpha8 is increased in pro-inflammatory conditions in both healthy controls and MS patients. Using methods for detecting alpha8 in tissues, researchers discovered that alpha8 is expressed on a subset of T-cells (CD3+ T cells) found throughout the brains of EAE mice, an animal MS model. Moreover, both BBB and BMB endothelial cells (ECs) containĀ the main binding partner of alpha8. By blocking the alpha8 binding site, the migratory ability of pro-inflammatory TH17 cells was seen to significantly decrease across an in vitro assay that mimicked ECs of the brain-blood barrier. Next, the researchers treated the EAE mice withĀ a compound toĀ block alpha8, and found it was able toĀ reduce the clinical severity, limit T-lymphocyte infiltration into the CNS, and prevent disease progression in the mouse model. “These data highlight an important role for alpha8 in mediating pro-inflammatory T lymphocyte migration across the CNS microvasculature, suggesting that this integrin may be an effective therapeutic target to prevent disease activity and progression in MS,” the researchers concluded in their ECTRIMS’ abstract. Print This Page About the Author Patricia Inacio, PhD Patricia holds her PhD in cell biology from the University Nova de Lisboa, Portugal, and has served as an author on several research projects and fellowships, as well as major grant applications for European agencies. She also served as a PhD student research assistant in the Department of Microbiology & Immunology, Columbia University, New York, for which she was awarded a Luso-American Development Foundation (FLAD) fellowship. Tags BBB, blood brain barrier, CNS, ECTRIMS2016, lymphocytes, migration, Th17 cells
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