Ligation of TLR7 on CD19+CD1dhi B cells suppresses allergic lung inflammation via regulatory T cells

Academic Article

Abstract

  • © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. B cells have been described as having the capacity to regulate cellular immune responses and suppress inflammatory processes. One such regulatory B-cell population is defined as IL-10-producing CD19+CD1dhi cells. Previous work has identified an expansion of these cells in mice infected with the helminth, Schistosoma mansoni. Here, microarray analysis of CD19+CD1dhi B cells from mice infected with S. mansoni demonstrated significantly increased Tlr7 expression, while CD19+CD1dhi B cells from uninfected mice also demonstrated elevated Tlr7 expression. Using IL-10 reporter, Il10-/- and Tlr7-/- mice, we formally demonstrate that TLR7 ligation of CD19+CD1dhi B cells increases their capacity to produce IL-10. In a mouse model of allergic lung inflammation, the adoptive transfer of TLR7-elicited CD19+CD1dhi B cells reduced airway inflammation and associated airway hyperresponsiveness. Using DEREG mice to deplete FoxP3+ T regulatory cells in allergen-sensitized mice, we show that that TLR7-elicited CD19+CD1dhi B cells suppress airway hyperresponsiveness via a T regulatory cell dependent mechanism. These studies identify that TLR7 stimulation leads to the expansion of IL-10-producing CD19+CD1dhi B cells, which can suppress allergic lung inflammation via T regulatory cells.
  • Published In

    Digital Object Identifier (doi)

    Pubmed Id

  • 12545598
  • Author List

  • Khan AR; Amu S; Saunders SP; Hams E; Blackshields G; Leonard MO; Weaver CT; Sparwasser T; Sheils O; Fallon PG
  • Start Page

  • 1842
  • End Page

  • 1854
  • Volume

  • 45
  • Issue

  • 6