CD4(+)c-Met(+)Itgα4(+) T cell subset promotes murine neuroinflammation

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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-022-02461-7.