Low frequency of IL-10+ B cells in patients with atherosclerosis is related with inflammatory condition

Abstract

Background and aims: B cells involvement in animal models of atherosclerosis has been unequivocally established. However, the role of these cells in patients with atherosclerosis is almost unknown. Besides the production of antibodies, B cells can also exhibit regulatory functions mainly through IL-10. Here, we characterized human B cell subsets, their production of IL-10 in patients with atherosclerosis and their potential association with inflammation. Methods: Patients with confirmed atherosclerotic events and controls with low cardiovascular risk were included. B cells subsets were determined in mononuclear cells (PBMC) using flow cytometry. PBMC were cultured ex vivo (5 h) and in vitro (48 h) to determine IL-10 þ B cells and in some cases TNF-α þ and IFN-γ þ CD4 þ T cells. The inflammatory state of the participants was determined through high sensitivity C reactive protein levels. Results: Increase in percentage and number of plasmablasts was observed in patients with atherosclerosis compared with controls. A decreased frequency of IL-10 þ B cells was observed in patients, both in ex vivo and in vitro cultures. This decrease was detected in transitional, memory, and plasmablast subsets. Interestingly, the reduction of IL-10 þ B cells negatively and significantly correlated with the inflammatory condition of the studied subjects and associated with an increased frequency of TNF-α þ and IFN-γ þ CD4 þ T cells. The blockade of IL-10R did not show further effect in T cells activation. Conclusions: There is an association between the inflammatory state and a reduction of IL-10 þ B cells that could contribute to the development of atherosclerosis.

Beyond Macrophages and T Cells: B Cells and Immunoglobulins Determine the Fate of the Atherosclerotic Plaque

“…A possible immune modulating role of angiotensin II remains to be investigated more in detail. Recently, also in human patients, active atherosclerotic vessel disease was brought into connection with decreased frequency of IL-10 + B cells [37]. In this study the low frequency of IL-10 + B cells correlated directly with a high inflammatory activity and an increased cardiovascular risk.…”

Inflammation and atherosclerosis: signaling pathways and therapeutic intervention

“…96 Besides the production of antibodies, B cells also play regulatory roles through the production of IL-10 and therefore these cells are named regulatory B cells. 97 , 98 Recent studies demonstrate that a low number of IL-10 + B cells in atherosclerosis patients is associated with inflammatory condition 99 and that alarmin-activated B cells accelerate atherosclerosis after myocardial infarction via plasma cell-immunoglobulin dependent mechanisms. 100 Hence, the identification of human B-cell subsets and their production of IL-10 would help to better understand the role of these cells in atherosclerosis, and to distinguish which of these subsets truly have a pro- or anti-atherogenic role (Fig.…”

Immunosuppressive Mechanisms of Regulatory B Cells

“…IL-10 + B cells have also been recovered from tertiary lymphoid organs in arteries of atherosclerotic mice, suggesting that in atherosclerosis (like in neuroinflammation), Bregs may also suppress inflammation in situ ( 217 ). In addition, scattered publications have reported reduced levels of transitional or IL-10 + B cells in peripheral blood of atherosclerotic patients compared to healthy controls ( 154 , 178 , 218 , 219 ). Furthermore, there is accumulating evidence pointing toward a protective role of IL-10-producing B cells in controlling inflammation and tissue damage following experimental ischemic stroke ( 220 – 225 ).…”