Disruption of a CD1d-mediated interaction between mast cells and NKT cells aggravates atherosclerosis

The development of atherosclerosis is tightly regulated by the innate and adaptive immune system. Communication between these two compartments occurs, among others, upon presentation of lipid antigens to the NKT cell population by CD1d-expressing antigen-presenting cells. Recent evidence states that also mast cells express CD1d and can directly communicate with NKT cells. However, no such relationship has been reported in atherosclerosis. Here, we aimed to elucidate in vivo the CD1d-mediated interaction between mast cells and NKT cells upon atherosclerosis progression.

We adoptively transferred CD1d^-/- or control mast cells to mast cell-deficient apoE^-/-Kit^W-sh/W-sh mice and subsequently placed the animals on a Western-type diet for 10 weeks.

At the end of the Western-type diet period, the aortic root of CD1d^-/- mast cell-reconstituted mice displayed increased plaque size, with less collagen deposition and higher intraplaque CD4⁺ T cells, as compared to control mice. In addition, T cells inside the aortic arch showed higher pro-inflammatory cytokine production in the form of IFNγ, TNFα and IL-17. Finally, T-bet expression was found elevated in both CD4⁺ and CD8⁺ circulating T cells.

This study is the first to illustrate that disruption of the CD1d communication pathway between mast cells and NKT cells aggravates atherosclerosis, through a shift towards pro-inflammatory T cell responses. This ability of mast cell action during plaque progression sheds new light on their role in atherosclerosis.