3 years ago

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

Eva Kritikou, Janine Van Duijn, Joya E. Nahon, Thomas Van Der Heijden, Merel Bouwman, Christianne Groeneveldt, Frank H. Schaftenaar, Mara J. Kröner, Johan Kuiper, Gijs H.m. Van Puijvelde, Ilze Bot

Publication date: Available online 14 November 2018

Source: Atherosclerosis

Author(s): Eva Kritikou, Janine van Duijn, Joya E. Nahon, Thomas van der Heijden, Merel Bouwman, Christianne Groeneveldt, Frank H. Schaftenaar, Mara J. Kröner, Johan Kuiper, Gijs H.M. van Puijvelde, Ilze Bot

Abstract
Background and aims

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.

Methods

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

Results

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.

Conclusions

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.

Graphical abstract

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