Intercellular Adhesion Molecule-1 (ICAM-1) and ICAM-2 Differentially Contribute to Peripheral Activation and CNS Entry of Autoaggressive Th1 and Th17 Cells in Experimental Autoimmune Encephalomyelitis.
In experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), myelin-specific T cells are activated in the periphery and differentiate in T helper (Th) 1 and Th17 effector cells, which cross the blood-brain barrier (BBB) to reach the central nervous system (CNS), where they induce neuroinflammation. Here, we explored the role of intercellular adhesion molecule-1 (ICAM-1) and ICAM-2 in the activation of naïve myelin-specific T cells and in the subsequent migration of differentiated encephalitogenic Th1 and Th17 cells across the BBB in vitro and in vivo. While on antigen-presenting cells ICAM-1, but not ICAM-2 was required for the activation of naïve CD4+ T cells, endothelial ICAM-1 and ICAM-2 mediated both Th1 and Th17 cell migration across the BBB. ICAM-1/-2-deficient mice developed ameliorated typical and atypical EAE transferred by encephalitogenic Th1 and Th17 cells, respectively. Our study underscores important yet cell-specific contributions for ICAM-1 and ICAM-2 in EAE pathogenesis.
['Haghayegh Jahromi|Neda|N|', 'Marchetti|Luca|L|', 'Moalli|Federica|F|', 'Duc|Donovan|D|', 'Basso|Camilla|C|', 'Tardent|Heidi|H|', 'Kaba|Elisa|E|', 'Deutsch|Urban|U|', 'Pot|Caroline|C|', 'Sallusto|Federica|F|', 'Stein|Jens V|JV|', 'Engelhardt|Britta|B|']
D000818:Animals D015703:Antigens, CD D001812:Blood-Brain Barrier D015815:Cell Adhesion Molecules D004681:Encephalomyelitis, Autoimmune, Experimental D018799:Intercellular Adhesion Molecule-1 D008213:Lymphocyte Activation D051379:Mice D008810:Mice, Inbred C57BL D018417:Th1 Cells D058504:Th17 Cells D057705:Transendothelial and Transepithelial Migration
ICAM-1 ICAM-2 Th17 cells experimental autoimmune encephalomyelitis blood-brain barrier T cell activation Th1 cells dendritic cells