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

Area of Science:

• Immunology
• Neuroscience
• Cell Biology

Background:

• The hepatocyte growth factor (HGF)/c-Met pathway regulates critical cellular functions.
• c-Met is a tyrosine kinase receptor essential for HGF signaling.
• CD4+ T cells play a role in autoimmune diseases like multiple sclerosis (MS).

Purpose of the Study:

• To investigate the role of c-Met expression in CD4+ T cells during experimental autoimmune encephalomyelitis (EAE), a mouse model of MS.
• To determine if CD4+ c-Met+ T cells are associated with disease pathogenesis and if they are present in human MS.

Main Methods:

• Flow cytometry and immunohistochemistry were used to analyze c-Met expression on CD4+ T cells from mice and human peripheral blood mononuclear cells (PBMCs).
• The in vivo function of CD4+ c-Met+ T cells was evaluated in the EAE model.
• Adoptive transfer experiments were performed using T cells with varying c-Met and integrin α4 (Itgα4) expression.

Main Results:

• CD4+ c-Met+ T cells in the central nervous system (CNS) during EAE exhibit a pro-inflammatory Th1/Th17 phenotype.
• These cells show increased adhesion and transmigration capabilities, linked to higher Itgα4 expression.
• Adoptive transfer of Itgα4-expressing CD4+ c-Met+ T cells exacerbated EAE severity.
• CD4+ c-Met+ T cells and elevated Itgα4 were found in the brains and blood of MS patients.

Conclusions:

• c-Met is expressed on pathogenic pro-inflammatory and pro-migratory CD4+ T lymphocytes.
• CD4+ c-Met+ T cells are associated with neuroinflammation in EAE and MS.
• c-Met may serve as a potential immune marker for highly pathogenic T cells in neuroinflammatory conditions.