Pristane attenuates atherosclerosis in Apoe-/- mice via IL-4-secreting regulatory plasma cell-mediated M2 macrophage polarization

Atherosclerosis, an inflammatory progressive vascular disease, causes heart disease and stroke worldwide. B cells with immune suppressive functions have been implicated in autoimmune, inflammatory, and cardiovascular diseases. However, the precise role of regulatory B cells and the interaction with macrophages in atherosclerosis remains undefined. In our study, eight-week-old female apolipoprotein E null (Apoe- /-) mice were treated with a single dose of vehicle or pristane and then placed on an atherogenic diet for 12 weeks. We found that pristane decreased atherosclerotic lesion formation and increased stability of atherosclerotic plaques in Apoe- /-mice. We also observed lower frequencies of CD19+ B cells but higher frequencies of CD138+ plasma cells and CD206+ M2 macrophages in Apoe-/-mice treated with pristane. Importantly, pristane inhibited immune cell infiltration into the vascular wall. The upregulation of IL-4 in bone-marrow CD138+ plasma cells from pristane-treated Apoe-/-mice was demonstrated by RNA-sequencing (RNA-seq). Consistently, oxidized low-density lipoprotein (oxLDL) directly induced IL-4-secreting plasma cell generation in vitro. In a co-culture system incubating an anti-IL-4 neutralizing antibody, the results showed that oxLDL-induced CD138+ plasma cells could boost M2 macro-phage polarization via IL-4 secretion. Our data demonstrate an unexpected role that pristane induces IL-4 -producing CD138+ regulatory plasma cell generation and M2 polarization to protect atherosclerosis development.

Automated summary

This study found that pristane can decrease atherosclerotic lesion formation and increase stability of plaques, while inhibiting the frequency of B cells and increasing the frequency of plasma cells and M2 macrophages. Pristane induces IL-4-producing CD138+ regulatory plasma cell generation, which promotes M2 macrophage polarization via IL-4 secretion.