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

J Neuroinflammation. 2022 Apr 29;19(1):103. doi: 10.1186/s12974-022-02461-7.


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.

Keywords: EAE; HGF; Integrin; MS; Neuroinflammation; T lymphocytes; Transmigration; c-Met.

MeSH terms

  • Animals
  • Encephalomyelitis, Autoimmune, Experimental* / pathology
  • Humans
  • Integrin alpha4
  • Mice
  • Mice, Inbred C57BL
  • Multiple Sclerosis* / pathology
  • Neuroinflammatory Diseases
  • Th17 Cells


  • Integrin alpha4