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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 demonstrated that CAD patients presented an inflammatory disorder in regulatory B cells, which could be used as a therapeutic target.

Stromal cell-derived factor-1 (SDF-1) plays critical roles in vascular development and hematopoiesis. Here, we investigated the function of SDF-1 rs1801157G/A polymorphism in various immune cells and examined its association with susceptibility to coronary artery disease (CAD). Protein and mRNA levels of SDF-1 were tested in peripheral CD4+ T cell, CD8+ T cells, monocytes, and natural killer (NK) T cells from healthy donors with different genotypes of rs1801157G/A polymorphism. Prevalence of the polymorphism was compared between CAD patients and healthy controls. Data revealed that SDF-1 mRNA and protein were detectable in CD4+ T cells, CD8+ T cells, monocytes and NK T cells. Interestingly, both protein level and mRNA level of SDF-1 were significantly increased in the monocytes with rs1801157AA genotype, whereas the same phenomenon was not observed in the other three cell types. Blockage of CD14 completely inhibited the upregulation of SDF-1 in the monocytes with rs1801157AA genotype. Association analysis showed that frequencies of the rs1801157AA genotype and A allele were significantly higher in CAD cases than in controls (odds ratio [OR] = 2.28, 95% confidence interval [CI], 1.50–3.29, p < 0.0001, and OR = 1.46, 95% CI, 1.21–3.73, p < 0.0001, respectively). Also, prevalence of rs1801157AA genotype was further increased in cases with ST-elevation myocardial infarction (OR = 1.65, 95% CI, 1.04–2.56, p = 0.028). Our data suggest a novel pathway for regulating SDF-1 and a new risk factor for CAD.

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

A high-density genetic map is essential for comparative genomic studies and fine mapping of QTL and can also facilitate genome sequence assembly. Here, a high density genetic map of Asian seabass was constructed with 3321 SNPs generated by sequencing 144 individuals in a F2 family. The length of the map was 1577.67 cM with an average marker interval of 0.52 cM. A high level of genomic synteny among Asian seabass, European seabass, Nile tilapia and stickleback was detected. Using this map, one genome-wide significant and five suggestive QTL for growth traits were detected in six linkage groups (i.e. LG4, LG5, LG11, LG13, LG14 and LG15). These QTL explained 10.5–16.0% of phenotypic variance. A candidate gene, ACOX1 within the significant QTL on LG5 was identified. The gene was differentially expressed between fast- and slow-growing Asian seabass. The high-density SNP-based map provides an important tool for fine mapping QTL in molecular breeding and comparative genome analysis.