CXCR7 mediates CD14+CD16+ monocyte transmigration across the blood brain barrier: a potential therapeutic target for NeuroAIDS
Title | CXCR7 mediates CD14+CD16+ monocyte transmigration across the blood brain barrier: a potential therapeutic target for NeuroAIDS |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Veenstra, M, Williams, DW, Calderon, TM, Anastos, K, Morgello, S, Berman, JW |
Journal | Journal of Leukocyte Biology |
Volume | 102 |
Start Page | 1173 |
Date Published | 11/2017 |
Abstract | CD14+CD16+ monocytes transmigrate into the CNS of HIV-positive people in response to chemokines elevated in the brains of infected individuals, including CXCL12. Entry of these cells leads to viral reservoirs, neuroinflammation, and neuronal damage. These may eventually lead to HIV-associated neurocognitive disorders. Although antiretroviral therapy (ART) has significantly improved the lives of HIV-infected people, the prevalence of cognitive deficits remains unchanged despite ART, still affecting .50% of infected individuals. There are no therapies to reduce these deficits or to prevent CNS entry of CD14+CD16+ monocytes. The goal of this study was to determine whether CXCR7, a receptor for CXCL12, is expressed on CD14+CD16+ monocytes and whether a small molecule CXCR7 antagonist (CCX771) can prevent CD14+CD16+ monocyte transmigration into the CNS. We showed for the first time that CXCR7 is on CD14+CD16+ monocytes and that it may be a therapeutic target to reduce their entry into the brain. We demonstrated that CD14+CD16+ monocytes and not the more abundant CD14+CD162 monocytes or T cells transmigrate to low homeostatic levels of CXCL12. This may be a result of increased CXCR7 on CD14+ |
URL | DOI: 10.1189/jlb.3HI0517-167R |