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B cells treated with CTB-p210 acquire a regulatory phenotype in vitro and reduce atherosclerosis in apolipoprotein E deficient mice

Author:
  • Sara Rattik
  • Polyxeni T. Mantani
  • Ingrid Yao Mattisson
  • Irena Ljungcrantz
  • Lena Sundius
  • Harry Björkbacka
  • Manuela Terrinoni
  • Michael Lebens
  • Jan Holmgren
  • Jan Nilsson
  • Maria Wigren
  • Gunilla Nordin Fredrikson
Publishing year: 2018-09-19
Language: English
Pages: 54-61
Publication/Series: Vascular Pharmacology
Volume: 111
Document type: Journal article
Publisher: Elsevier

Abstract english

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 Apobtm2Sgyldlr−/− or Apoe−/− mice with CTB-p210 for 1 h and co-culturing them with naïve T cells for 48 h, we observed increased expression of membrane bound TGFβ/latency-associated peptide (mTGFβ/LAP) on B cells and an increased proportion of CD25hiFoxP3+ 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.

Keywords

  • Cardiac and Cardiovascular Systems
  • Atherosclerosis
  • Regulatory B cells
  • Regulatory T cells
  • Tolerance

Other

Published
  • Cardiovascular Research - Immunity and Athersosclerosis
  • Cardiovascular Research - Cellular Metabolism and Inflammation
  • ISSN: 1537-1891
E-mail: lena [dot] sundius [at] med [dot] lu [dot] se

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