Dipeptidyl Peptidase 4/Midline-1 Axis Promotes T Lymphocyte Motility in Atherosclerosis

Area of Science:

• Immunology
• Cardiovascular Research
• Molecular Biology

Background:

• T cells are integral to atherosclerosis development, but their infiltration regulation is unclear.
• Understanding T-cell regulation is crucial for developing atherosclerosis therapies.

Purpose of the Study:

• To identify novel regulators of T-cell motility in atherosclerosis.
• To investigate the role of dipeptidyl peptidase-4 (DPP4) in T-cell infiltration and atherosclerosis.

Main Methods:

• Single-cell RNA sequencing and flow cytometry were used to analyze T cells from atherosclerotic patients.
• Atherosclerosis mouse models with genetic modifications (DPP4 or Mid1 deletion) were employed.
• Chemokine-induced T-cell motility and shape change assays were performed.

Main Results:

• CD4+ T cells in atherosclerotic patients showed increased DPP4 expression.
• DPP4 deficiency in hematopoietic or T cells reduced T-cell infiltration and atherosclerotic plaque volume in mice.
• DPP4 deficiency suppressed T-cell motility by reducing Mid1 expression, impacting shape change and migration.

Conclusions:

• Dipeptidyl peptidase-4 (DPP4) is a novel regulator of T-cell motility in atherosclerosis.
• The DPP4/Mid1 pathway influences T-cell infiltration and atherosclerotic plaque progression.
• Targeting DPP4/Mid1 may offer a new therapeutic strategy for atherosclerosis.