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

Adnan R. Khan, Sylvie Amu, Sean P. Saunders, Emily Hams, Gordon Blackshields, Martin Leonard, Casey T. Weaver, Tim Sparwasser, Orla Sheils, Padraic G. Fallon

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1842-1854
Number of pages13
JournalEuropean Journal of Immunology
Volume45
Issue number6
DOIs
Publication statusPublished - 1 Jun 2015

Keywords

  • AHR
  • Helminth
  • IL-10
  • Regulatory B cells
  • TLR7 Treg cells

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