Pro-Inflammatory c-Met⁺ CD4 T Cells in Multiple Sclerosis

Area of Science:

• Immunology
• Neuroscience
• Cell Biology

Background:

• The HGF/c-Met axis plays a role in T cell function and autoimmune diseases.
• Understanding CD4 T cell involvement in multiple sclerosis (MS) is crucial.

Purpose of the Study:

• To analyze c-Met expression on CD4 T cells in the blood and cerebrospinal fluid (CSF) of MS patients compared to non-inflammatory neurological disease (NIND) patients.
• To characterize the function and inflammatory potential of c-Met positive CD4 T cells in MS.

Main Methods:

• Recruited 34 untreated MS patients and 13 NIND patients for paired blood and CSF sampling.
• Utilized flow cytometry and bulk RNA sequencing for CD4 T cell characterization.
• Assessed adhesion and transmigration capacities of c-Met positive CD4 T cells.

Main Results:

• c-Met positive memory CD4 T cells were significantly higher in both blood and CSF of MS patients compared to NIND patients.
• Ex vivo c-Met positive CD4 T cells showed increased expression of pro-inflammatory cytokines (GM-CSF, IL-17, IFN-γ) and integrins (VLA-4, LFA-1).
• Inhibition of integrins α4 and αLβ2 reduced CD4 T cell transmigration, particularly for c-Met positive cells.

Conclusions:

• c-Met serves as an immune marker for highly pro-inflammatory and migratory CD4 T lymphocytes.
• These findings highlight the role of c-Met positive CD4 T cells in both the periphery and central nervous system in MS pathogenesis.
• c-Met expression on CD4 T cells offers a potential therapeutic target in multiple sclerosis.