The CD1d-Natural Killer T Cell Axis in Atherosclerosis

Abstract

A key role for ‘lipid-sensing' CD1-restricted natural killer T (NKT) cells in the pathogenesis of atherosclerosis has been suggested. However, the biology of NKT cells remains poorly characterized, as in different experimental settings their activation was reported to both stimulate and suppress innate and adaptive immune responses. Most of the data from experimental models suggest that NKT cells are proatherogenic; however, it is debated whether the increase in atherosclerosis observed following NKT cell stimulation is a consequence of the inability to induce functional NKT cells rather than the proatherogenic nature of NKT cells. CD1d-expressing antigen-presenting cells and NKT cells were detected in mouse and human atherosclerotic lesions. Furthermore, several lysophospholipids and glycosphingolipids, known to accumulate in atherosclerotic plaques, are antigenic for human NKT cell clones. Lipid transfer proteins, such as apolipoprotein E and microsomal triglyceride transfer protein, are central to NKT cell responses. All these data suggest a profound relation between lipid metabolism, CD1d-NKT cell axis activation and atherosclerosis. In this review, we summarize the advances and gaps in our knowledge of NKT cell biology in the context of atherosclerosis as well as the possibility of influencing NKT cell polarization toward an atheroprotective phenotype.

Regulation of NKT cell-mediated immune responses to tumours and liver inflammation by mitochondrial PGAM5-Drp1 signalling

“…For example, NKT cells promote the immune response to tumours and microbial infections, while suppressing immune responses in autoimmune diseases such as acute hepatitis and arthritis 21 22 23 . Furthermore, NKT cell activation can be harmful to the host in some inflammatory diseases such as atherosclerosis 24 . Despite their paradoxical functions in different disease conditions, NKT cells clearly play a crucial role in regulating the pathogenesis of various diseases.…”

An overview of the innate and adaptive immune system in atherosclerosis

“…273 The iNKT cells, similar to CD8 + T cells, can express cytotoxic proteins such as granzyme and perforin. 274 Most researches performed on mice indicated that iNKT cells play a pro-atherogenic role. 275 The iNKT cells can activate immune cells in plaque, by secreting cytokines and promoting atherosclerosis development.…”

Immune Disorder in Atherosclerotic Cardiovascular Disease ― Clinical Implications of Using Circulating T-Cell Subsets as Biomarkers ―

“…7 Adaptive immunity is further divided into (1) humoral immunity, which is mediated by B cells and antibodies; and (2) cellmediated immunity, which is mediated by T cells that activate macrophages for killing or that lyse infected cells. 15,16 T lymphocytes are characterized by a surface CD3 and consist of two major functional subsets: T-helper (Th) lymphocytes expressing the cell-surface molecule CD4, and cytotoxic T lymphocytes (CTL) expressing the cell-surface molecule CD8. The γ δT cells, however, are another T-cell subset: they have γ δTCR and are negative for CD4 and CD8, and they have CD277 as the antigenpresenting molecule.…”