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), wh...
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| Format: | Article |
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Frontiers Media S.A.
2020-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.03056/full |
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| author | Neda Haghayegh Jahromi Luca Marchetti Federica Moalli Donovan Duc Camilla Basso Heidi Tardent Elisa Kaba Urban Deutsch Caroline Pot Federica Sallusto Federica Sallusto Jens V. Stein Britta Engelhardt |
| author_facet | Neda Haghayegh Jahromi Luca Marchetti Federica Moalli Donovan Duc Camilla Basso Heidi Tardent Elisa Kaba Urban Deutsch Caroline Pot Federica Sallusto Federica Sallusto Jens V. Stein Britta Engelhardt |
| author_sort | Neda Haghayegh Jahromi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T02:48:10Z |
| format | Article |
| id | doaj.art-1892b1576fe14ed993834d7fed2d5ea3 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-20T02:48:10Z |
| publishDate | 2020-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-1892b1576fe14ed993834d7fed2d5ea32022-12-21T19:56:07ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-01-011010.3389/fimmu.2019.03056509953Intercellular 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 EncephalomyelitisNeda Haghayegh Jahromi0Luca Marchetti1Federica Moalli2Donovan Duc3Camilla Basso4Heidi Tardent5Elisa Kaba6Urban Deutsch7Caroline Pot8Federica Sallusto9Federica Sallusto10Jens V. Stein11Britta Engelhardt12Theodor Kocher Institute, University of Bern, Bern, SwitzerlandTheodor Kocher Institute, University of Bern, Bern, SwitzerlandTheodor Kocher Institute, University of Bern, Bern, SwitzerlandLaboratories of Neuroimmunology, Division of Neurology and Neuroscience Research Center, Department of Clinical Neurosciences, Lausanne University Hospital, University of Lausanne, Epalinges, SwitzerlandInstitute for Research in Biomedicine, Università della Svizzera Italiana, Bellinzona, SwitzerlandTheodor Kocher Institute, University of Bern, Bern, SwitzerlandTheodor Kocher Institute, University of Bern, Bern, SwitzerlandTheodor Kocher Institute, University of Bern, Bern, SwitzerlandLaboratories of Neuroimmunology, Division of Neurology and Neuroscience Research Center, Department of Clinical Neurosciences, Lausanne University Hospital, University of Lausanne, Epalinges, SwitzerlandInstitute for Research in Biomedicine, Università della Svizzera Italiana, Bellinzona, SwitzerlandDepartment of Biology, Institute of Microbiology, ETH Zurich, Zurich, SwitzerlandTheodor Kocher Institute, University of Bern, Bern, SwitzerlandTheodor Kocher Institute, University of Bern, Bern, SwitzerlandIn 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.https://www.frontiersin.org/article/10.3389/fimmu.2019.03056/fullexperimental autoimmune encephalomyelitisICAM-1ICAM-2dendritic cellsTh1 cellsTh17 cells |
| spellingShingle | Neda Haghayegh Jahromi Luca Marchetti Federica Moalli Donovan Duc Camilla Basso Heidi Tardent Elisa Kaba Urban Deutsch Caroline Pot Federica Sallusto Federica Sallusto Jens V. Stein Britta Engelhardt 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 Frontiers in Immunology experimental autoimmune encephalomyelitis ICAM-1 ICAM-2 dendritic cells Th1 cells Th17 cells |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | experimental autoimmune encephalomyelitis ICAM-1 ICAM-2 dendritic cells Th1 cells Th17 cells |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.03056/full |
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