Tim ‐1+ B cells suppress T cell interferon‐gamma production and promote Foxp3 expression, but have impaired regulatory function in coronary artery disease

Atherosclerosis and its associated coronary artery disease (CAD) represent another chronic low‐grade inflammatory disorder. Regulatory B cells (Bregs) possess essential functions in maintaining peripheral tolerance and inhibiting pathogenic inflammation through IL‐10. Here, we investigated one subset of Bregs, Tim‐1+ B cell, and its role in atherosclerosis and CAD patients. In healthy individuals, IL‐10‐producing B cells were predominantly found in the Tim‐1+ B cells. Upon stimulation of the B cell receptor (BCR) and Toll‐like receptor 9 (TLR‐9) by anti‐BCR antibodies and CpG, respectively, the Tim‐1+ B cells could further upregulate IL‐10 expression. In contrast, the Tim‐1+ B cells were present at normal frequency in CAD patients, but showed impaired capacity to upregulate IL‐10 with or without BCR + CpG stimulation. The stimulated Tim‐1+ B cells from healthy individuals also suppressed expression of interferon gamma (IFN‐γ), an atherogenic cytokine in T cells, in an IL‐10‐dependent fashion, and strongly promoted the expression of Foxp3 in naive CD4+CD45RO− T cells. In contrast, the Tim‐1+ B cells from CAD patients were unable to suppress IFN‐γ secretion, and only minimally increased the expression of Foxp3 in naive CD4+CD45RO− T cells. Despite this, the frequency of Tim‐1+ B cells in the atherosclerotic lesions from CAD patients was inversely correlated with the frequency of IFN‐γ‐expressing T cells. Together, these results...

Source: APMIS - July 24, 2017 Category: Research Authors: Xiao ‐Long Gu, Huan He, Lin Lin, Guo‐Xin Luo, Yan‐Fei Wen, Ding‐Cheng Xiang, Jian Qiu Tags: Original Article Source Type: research