title: Peripheral T cells derived from Alzheimer's disease patients overexpress CXCR2 contributing to its transendothelial migration, which is microglial TNF-alpha-dependent.
abstract: The mechanism of circulating T cells entry into the brain in Alzheimer's diseases (AD) remains unclear. Here, we showed that peripheral T cells derived from AD patients overexpress CXCR2 to enhance its transendothelial migration. T cells migration through in vitro blood-brain barrier model was effectively blocked by anti-CXCR2 antibody or IL-8 (a CXCR2 ligand) RNAi in human brain microvascular endothelial cells (HBMECs). Amyloid beta (Abeta) injection in rat hippocampus upregulated CXCR2 expression accompanied with increased T cells occurrence in the brain, and this enhanced T cells entry was effectively blocked by CXCR2 antagonist. Furthermore, anti-TNF-alpha antibody blocked IL-8 production in HBMECs and T cells transendothelial migration caused by the culture supernatant of microglia treated with Abeta. Blockage of intracerebral TNF-alpha abolished the upregulation of CXCR2 in peripheral T cells and the increased T cells occurrence in the brain induced by Abeta injection in rat hippocampus. These data suggest that CXCR2 overexpression in peripheral T cells is intracerebral microglial TNF-alpha-dependent and TNF-alpha primes T cells transendothelial migration in Alzheimer's diseases.
authors.affiliation: Department of Developmental Biology, Key Laboratory of Cell Biology, Ministry of Public Health of China, China Medical University, Shenyang 110001, PR China.
authors.forename: Yi-Jun
authors.initials: YJ
authors.lastname: Liu
authors.forename: Da-Wen
authors.initials: DW
authors.lastname: Guo
authors.forename: Li
authors.initials: L
authors.lastname: Tian
authors.forename: De-Shu
authors.initials: DS
authors.lastname: Shang
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Zhao
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.forename: Wen-Gang
authors.initials: WG
authors.lastname: Fang
authors.forename: Li
authors.initials: L
authors.lastname: Zhu
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Chen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001323:Autoantibodies / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000503:physiopathology*; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000378:metabolism; D055806:Microvessels / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D023063:Receptors, Interleukin-8B / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D001323:Autoantibodies; D016209:Interleukin-8; D023063:Receptors, Interleukin-8B; D014409:Tumor Necrosis Factor-alpha