The CD1d-natural killer T cell axis in atherosclerosis

Area of Science:

• Immunology
• Cardiovascular Disease
• Lipid Metabolism

Background:

• The role of lipid-sensing CD1-restricted natural killer T (NKT) cells in atherosclerosis pathogenesis is suggested but poorly understood.
• NKT cell activation has shown conflicting effects, stimulating or suppressing immune responses, with experimental models often indicating a proatherogenic role.
• Debate exists on whether observed atherosclerosis increases are due to NKT cell dysfunction or their inherent proatherogenic nature.

Purpose of the Study:

• To review current knowledge on NKT cell biology in atherosclerosis.
• To identify gaps in understanding the NKT cell-atherosclerosis connection.
• To explore strategies for modulating NKT cell polarization towards an atheroprotective phenotype.

Main Methods:

• Review of existing literature on NKT cells, CD1d antigen presentation, and lipid metabolism in atherosclerosis.
• Analysis of studies detecting CD1d-expressing cells and NKT cells in atherosclerotic lesions (mouse and human).
• Examination of antigenic properties of lipids found in atherosclerotic plaques for NKT cell clones.

Main Results:

• CD1d-expressing antigen-presenting cells and NKT cells are present in atherosclerotic lesions.
• Lysophospholipids and glycosphingolipids accumulating in plaques are antigenic for NKT cells.
• Lipid transfer proteins (e.g., ApoE, MTP) are crucial for NKT cell responses.

Conclusions:

• A strong link exists between lipid metabolism, CD1d-NKT cell axis activation, and atherosclerosis.
• Further research is needed to clarify NKT cell functions in atherosclerosis.
• Targeting NKT cell polarization may offer a therapeutic avenue for atherosclerosis.