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

Author:
  • Asa C. Strom
  • Amanda J. Cross
  • Jennifer E. Cole
  • Paul A. Blair
  • Christoph Leib
  • Michael E. Goddard
  • Elizabeth C. Rosser
  • Inhye Park
  • Anna Hultgardh Nilsson
  • Jan Nilsson
  • Claudia Mauri
  • Claudia Monaco
Publishing year: 2015
Language: English
Pages: 835-847
Publication/Series: Thrombosis and Haemostasis
Volume: 114
Issue: 4
Document type: Journal article
Publisher: F K Schattauer Verlag Gmbh

Abstract english

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.

Keywords

  • Cardiac and Cardiovascular Systems
  • Immunology in the medical area
  • Immunity
  • B regulatory cells
  • interleukins
  • atherosclerosis
  • vascular
  • disease

Other

Published
  • Cardiovascular Research - Immunity and Atherosclerosis
  • ISSN: 0340-6245
E-mail: jan [dot] nilsson [at] med [dot] lu [dot] se

Lund University Diabetes Centre, CRC, SUS Malmö, Jan Waldenströms gata 35, House 91:12. SE-214 28 Malmö. Telephone: +46 40 39 10 00