CD4+c-Met+Itgα4+ T cell subset promotes murine neuroinflammation
Abstract Objective c-Met, a tyrosine kinase receptor, is the unique receptor for hepatocyte growth factor (HGF). The HGF/c-Met axis is reported to modulate cell migration, maturation, cytokine production, and antigen presentation. Here, we report that CD4+c-Met+ T cells are detected at increased lev...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-04-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12974-022-02461-7 |
| _version_ | 1818266787193552896 |
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| author | Mahdia Benkhoucha Ngoc Lan Tran Gautier Breville Isis Senoner Paul F. Bradfield Thalia Papayannopoulou Doron Merkler Thomas Korn Patrice H. Lalive |
| author_facet | Mahdia Benkhoucha Ngoc Lan Tran Gautier Breville Isis Senoner Paul F. Bradfield Thalia Papayannopoulou Doron Merkler Thomas Korn Patrice H. Lalive |
| author_sort | Mahdia Benkhoucha |
| collection | DOAJ |
| description | Abstract Objective c-Met, a tyrosine kinase receptor, is the unique receptor for hepatocyte growth factor (HGF). The HGF/c-Met axis is reported to modulate cell migration, maturation, cytokine production, and antigen presentation. Here, we report that CD4+c-Met+ T cells are detected at increased levels in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS). Methods c-Met expression by CD4+ T cells was analyzed mostly by flow cytometry and by immunohistochemistry from mice and human PBMCs. The in vivo role of CD4+c-Met+ T cells was assessed in EAE. Results CD4+c-Met+ T cells found in the CNS during EAE peak disease are characterized by a pro-inflammatory phenotype skewed towards a Th1 and Th17 polarization, with enhanced adhesion and transmigration capacities correlating with increased expression of integrin α4 (Itgα4). The adoptive transfer of Itgα4-expressing CD4+Vα3.2+c-Met+ T cells induces increased disease severity compared to CD4+Vα3.2+c-Met− T cells. Finally, CD4+c-Met+ T cells are detected in the brain of MS patients, as well as in the blood with a higher level of Itgα4. These results highlight c-Met as an immune marker of highly pathogenic pro-inflammatory and pro-migratory CD4+ T lymphocytes associated with neuroinflammation. |
| first_indexed | 2024-12-12T20:12:15Z |
| format | Article |
| id | doaj.art-a6b2cea755e146b8bff23ade4c459ccc |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-12-12T20:12:15Z |
| publishDate | 2022-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-a6b2cea755e146b8bff23ade4c459ccc2022-12-22T00:13:29ZengBMCJournal of Neuroinflammation1742-20942022-04-0119111910.1186/s12974-022-02461-7CD4+c-Met+Itgα4+ T cell subset promotes murine neuroinflammationMahdia Benkhoucha0Ngoc Lan Tran1Gautier Breville2Isis Senoner3Paul F. Bradfield4Thalia Papayannopoulou5Doron Merkler6Thomas Korn7Patrice H. Lalive8Department of Pathology and Immunology, Faculty of Medicine, University of GenevaDepartment of Pathology and Immunology, Faculty of Medicine, University of GenevaDepartment of Pathology and Immunology, Faculty of Medicine, University of GenevaDepartment of Pathology and Immunology, Faculty of Medicine, University of GenevaMesenFlow Technologies SARLDivision of Hematology, Department of Medicine, University of WashingtonDivision of Clinical Pathology, Department of Pathology and Immunology, Faculty of Medicine, University of GenevaDepartment of Neurology, Klinikum rechts der Isar, Technical University of MunichDepartment of Pathology and Immunology, Faculty of Medicine, University of GenevaAbstract Objective c-Met, a tyrosine kinase receptor, is the unique receptor for hepatocyte growth factor (HGF). The HGF/c-Met axis is reported to modulate cell migration, maturation, cytokine production, and antigen presentation. Here, we report that CD4+c-Met+ T cells are detected at increased levels in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS). Methods c-Met expression by CD4+ T cells was analyzed mostly by flow cytometry and by immunohistochemistry from mice and human PBMCs. The in vivo role of CD4+c-Met+ T cells was assessed in EAE. Results CD4+c-Met+ T cells found in the CNS during EAE peak disease are characterized by a pro-inflammatory phenotype skewed towards a Th1 and Th17 polarization, with enhanced adhesion and transmigration capacities correlating with increased expression of integrin α4 (Itgα4). The adoptive transfer of Itgα4-expressing CD4+Vα3.2+c-Met+ T cells induces increased disease severity compared to CD4+Vα3.2+c-Met− T cells. Finally, CD4+c-Met+ T cells are detected in the brain of MS patients, as well as in the blood with a higher level of Itgα4. These results highlight c-Met as an immune marker of highly pathogenic pro-inflammatory and pro-migratory CD4+ T lymphocytes associated with neuroinflammation.https://doi.org/10.1186/s12974-022-02461-7c-MetHGFT lymphocytesIntegrinTransmigrationNeuroinflammation |
| spellingShingle | Mahdia Benkhoucha Ngoc Lan Tran Gautier Breville Isis Senoner Paul F. Bradfield Thalia Papayannopoulou Doron Merkler Thomas Korn Patrice H. Lalive CD4+c-Met+Itgα4+ T cell subset promotes murine neuroinflammation Journal of Neuroinflammation c-Met HGF T lymphocytes Integrin Transmigration Neuroinflammation |
| title | CD4+c-Met+Itgα4+ T cell subset promotes murine neuroinflammation |
| title_full | CD4+c-Met+Itgα4+ T cell subset promotes murine neuroinflammation |
| title_fullStr | CD4+c-Met+Itgα4+ T cell subset promotes murine neuroinflammation |
| title_full_unstemmed | CD4+c-Met+Itgα4+ T cell subset promotes murine neuroinflammation |
| title_short | CD4+c-Met+Itgα4+ T cell subset promotes murine neuroinflammation |
| title_sort | cd4 c met itgα4 t cell subset promotes murine neuroinflammation |
| topic | c-Met HGF T lymphocytes Integrin Transmigration Neuroinflammation |
| url | https://doi.org/10.1186/s12974-022-02461-7 |
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