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

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

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)835-847
JournalThrombosis and Haemostasis
Volume114
Issue number4
DOIs
Publication statusPublished - 2015

Subject classification (UKÄ)

  • Cardiac and Cardiovascular Systems
  • Immunology in the medical area

Free keywords

  • Immunity
  • B regulatory cells
  • interleukins
  • atherosclerosis
  • vascular
  • disease

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