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

Rattik, Sara LU ; Mantani, Polyxeni T. LU ; Yao Mattisson, Ingrid LU ; Ljungcrantz, Irena LU ; Sundius, Lena LU ; Björkbacka, Harry LU ; Terrinoni, Manuela; Lebens, Michael; Holmgren, Jan and Nilsson, Jan LU , et al. (2018) In Vascular Pharmacology2002-01-01+01:00 111. p.54-61
Abstract

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... (More)

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.

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publication status
published
subject
keywords
Atherosclerosis, Regulatory B cells, Regulatory T cells, Tolerance
in
Vascular Pharmacology2002-01-01+01:00
volume
111
pages
54 - 61
publisher
Elsevier
external identifiers
  • scopus:85054176765
ISSN
1537-1891
DOI
10.1016/j.vph.2018.09.002
language
English
LU publication?
yes
id
e116e972-d1bb-44c3-993d-a91f6f6c74c7
date added to LUP
2018-10-22 10:31:00
date last changed
2019-01-14 16:20:57
@article{e116e972-d1bb-44c3-993d-a91f6f6c74c7,
  abstract     = {<p>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<sup>tm2Sgy</sup>ldlr<sup>−/−</sup> or Apoe<sup>−/−</sup> 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 CD25<sup>hi</sup>FoxP3<sup>+</sup> Tregs. Adoptive transfer of B cells pulsed with CTB-p210 into high-fat diet-fed Apoe<sup>−/−</sup> 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<sup>−/−</sup> mice decreased atherosclerosis development.</p>},
  author       = {Rattik, Sara and Mantani, Polyxeni T. and Yao Mattisson, Ingrid and Ljungcrantz, Irena and Sundius, Lena and Björkbacka, Harry and Terrinoni, Manuela and Lebens, Michael and Holmgren, Jan and Nilsson, Jan and Wigren, Maria and Nordin Fredrikson, Gunilla},
  issn         = {1537-1891},
  keyword      = {Atherosclerosis,Regulatory B cells,Regulatory T cells,Tolerance},
  language     = {eng},
  month        = {09},
  pages        = {54--61},
  publisher    = {Elsevier},
  series       = {Vascular Pharmacology2002-01-01+01:00},
  title        = {B cells treated with CTB-p210 acquire a regulatory phenotype in vitro and reduce atherosclerosis in apolipoprotein E deficient mice},
  url          = {http://dx.doi.org/10.1016/j.vph.2018.09.002},
  volume       = {111},
  year         = {2018},
}