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B regulatory cells are increased in hypercholesterolaemic mice and protect from lesion development via IL-10

Strom, Asa C.; Cross, Amanda J.; Cole, Jennifer E.; Blair, Paul A.; Leib, Christoph; Goddard, Michael E.; Rosser, Elizabeth C.; Park, Inhye; Nilsson, Anna Hultgardh and Nilsson, Jan LU , et al. (2015) In Thrombosis and Haemostasis 114(4). p.835-847
Abstract
Whilst innate B1-B cells are atheroprotective, adaptive B2-B cells are considered pro-atherogenic. Different subsets of B regulatory cells (B-reg) have been described. In experimental arthritis and lupus-like disease, B-reg are contained within the CD21(hi)CD23(hi)CD24(hi) B cell pool The existence and role of B-reg in vascular disease is not known. We sought to investigate the existence, identity and location of B-reg in vascular disease. The representation of B2-B cell subsets in the spleens and lymph nodes (LNs) of Apolipoprotein E-/- (ApoE(-/-)) mice compared to controls was characterised by flow cytometry. Additionally, we utilised a model of neointima formation based on the placement of a perivascular collar around the carotid artery... (More)
Whilst innate B1-B cells are atheroprotective, adaptive B2-B cells are considered pro-atherogenic. Different subsets of B regulatory cells (B-reg) have been described. In experimental arthritis and lupus-like disease, B-reg are contained within the CD21(hi)CD23(hi)CD24(hi) B cell pool The existence and role of B-reg in vascular disease is not known. We sought to investigate the existence, identity and location of B-reg in vascular disease. The representation of B2-B cell subsets in the spleens and lymph nodes (LNs) of Apolipoprotein E-/- (ApoE(-/-)) mice compared to controls was characterised by flow cytometry. Additionally, we utilised a model of neointima formation based on the placement of a perivascular collar around the carotid artery in ApoE(-/-) mice to ascertain whether B cells and B cell subsets confer protection against lesion development. Adoptive transfer of B cells was performed from wild type or genetically modified mice. We showed that CD21(hi)CD23(hi)CD24(hi) B cells are unexpectedly increased in the draining LNs of ApoE(-/-) mice. Adoptive transfer of LN-derived B2-B cells or purified CD21(hi)CD23(hi)CD24(hi) B cells to syngeneic mice reduced lesion size and inflammation without changing serum cholesterol levels. Follicular B2-B cells did not confer protection. IL-10 blockade or transfer of IL10-deficient B cells prevented LN-derived B cell-mediated protection. This is the first identification of a specific LN-derived B2-B-reg subset that confers IL-10 mediated protection from neointima formation. This may open the way for immune modulatory approaches in cardiovascular disease. (Less)
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publishing date
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Contribution to journal
publication status
published
subject
keywords
Immunity, B regulatory cells, interleukins, atherosclerosis, vascular, disease
in
Thrombosis and Haemostasis
volume
114
issue
4
pages
835 - 847
publisher
F K Schattauer Verlag Gmbh
external identifiers
  • wos:000362144300021
  • scopus:84943192416
ISSN
0340-6245
DOI
10.1160/TH14-12-1084
language
English
LU publication?
yes
id
5c605b47-2e39-4d8f-b26e-31119ecb78f6 (old id 8223859)
date added to LUP
2015-12-01 11:57:13
date last changed
2017-11-12 03:33:36
@article{5c605b47-2e39-4d8f-b26e-31119ecb78f6,
  abstract     = {Whilst innate B1-B cells are atheroprotective, adaptive B2-B cells are considered pro-atherogenic. Different subsets of B regulatory cells (B-reg) have been described. In experimental arthritis and lupus-like disease, B-reg are contained within the CD21(hi)CD23(hi)CD24(hi) B cell pool The existence and role of B-reg in vascular disease is not known. We sought to investigate the existence, identity and location of B-reg in vascular disease. The representation of B2-B cell subsets in the spleens and lymph nodes (LNs) of Apolipoprotein E-/- (ApoE(-/-)) mice compared to controls was characterised by flow cytometry. Additionally, we utilised a model of neointima formation based on the placement of a perivascular collar around the carotid artery in ApoE(-/-) mice to ascertain whether B cells and B cell subsets confer protection against lesion development. Adoptive transfer of B cells was performed from wild type or genetically modified mice. We showed that CD21(hi)CD23(hi)CD24(hi) B cells are unexpectedly increased in the draining LNs of ApoE(-/-) mice. Adoptive transfer of LN-derived B2-B cells or purified CD21(hi)CD23(hi)CD24(hi) B cells to syngeneic mice reduced lesion size and inflammation without changing serum cholesterol levels. Follicular B2-B cells did not confer protection. IL-10 blockade or transfer of IL10-deficient B cells prevented LN-derived B cell-mediated protection. This is the first identification of a specific LN-derived B2-B-reg subset that confers IL-10 mediated protection from neointima formation. This may open the way for immune modulatory approaches in cardiovascular disease.},
  author       = {Strom, Asa C. and Cross, Amanda J. and Cole, Jennifer E. and Blair, Paul A. and Leib, Christoph and Goddard, Michael E. and Rosser, Elizabeth C. and Park, Inhye and Nilsson, Anna Hultgardh and Nilsson, Jan and Mauri, Claudia and Monaco, Claudia},
  issn         = {0340-6245},
  keyword      = {Immunity,B regulatory cells,interleukins,atherosclerosis,vascular,disease},
  language     = {eng},
  number       = {4},
  pages        = {835--847},
  publisher    = {F K Schattauer Verlag Gmbh},
  series       = {Thrombosis and Haemostasis},
  title        = {B regulatory cells are increased in hypercholesterolaemic mice and protect from lesion development via IL-10},
  url          = {http://dx.doi.org/10.1160/TH14-12-1084},
  volume       = {114},
  year         = {2015},
}