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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
  • 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
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Kardiologi
  • Immunologi inom det medicinska området

Nyckelord

Originalspråkengelska
Sidor (från-till)835-847
TidskriftThrombosis and Haemostasis
Volym114
Utgivningsnummer4
StatusPublished - 2015
PublikationskategoriForskning
Peer review utfördJa