期刊
VASCULAR PHARMACOLOGY
卷 111, 期 -, 页码 54-61出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.vph.2018.09.002
关键词
Atherosclerosis; Regulatory B cells; Tolerance; Regulatory T cells
资金
- Swedish Medical Research Council
- Swedish Heart-Lung foundation
- Albert Pahlsson foundation
- Swedish Foundation for Strategic Research
- European Union [603131, HEALTH-F2-2013-602114]
Objective: Intranasal immunization with a fusion protein of the ApoB100-derived peptide p210 and the cholera toxin B subunit (CTB-p210) has previously been shown to induce mucosal tolerance and reduce atherosclerosis development, but the exact mode of action remains to be elucidated. Recent studies have indicated an important role for B cells in mucosal tolerance, in particular by induction of regulatory B (Bregs) and T cells (Tregs). In this study, we aimed to investigate if transfer of B cells pulsed with CTB-p210 can protect against atherosclerosis. Method and results: First, we studied if CTB-p210 can induce Bregs and Tregs in vitro. After pulsing B cells from Apob(tm2gy)ldlr(-/-) or Apoe(-/-) mice with CTB-p210 for 1 h and co-culturing them with naive T cells for 48 h, we observed increased expression of membrane bound TGF beta/latency-associated peptide (mTGF beta/LAP) on B cells and an increased proportion of CD25(hi)FoxP3(+) Tregs. Adoptive transfer of B cells pulsed with CTB-p210 into high-fat diet-fed Apoe(-/-) mice at 8, 10 and 12 weeks of age, reduced the plaque area in the aorta at 20 weeks of age as compared with control-treated (CTB-pOVA treated B cells or PBS) mice. Moreover, mice receiving p210-CTB treated B cells had increased levels of anti-p210 IgG antibodies. Conclusion: Our observations suggest that CTB-p210 pulsed B cells acquire a regulatory phenotype and induce Tregs in vitro. Adoptive transfer of CTB-p210, but not control-treated, B cells into Apoe(-/-) mice decreased atherosclerosis development.
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