Ligation of TLR7 on CD19+CD1dhi B cells suppresses allergic lung inflammation via regulatory T cells. Issue 6 (14th April 2015)

• Record Type: Journal Article
• Authors: Khan, Adnan R.; Amu, Sylvie; Saunders, Sean P.; Hams, Emily; Blackshields, Gordon; Leonard, Martin O.; Weaver, Casey T.; Sparwasser, Tim; Sheils, Orla; Fallon, Padraic G.
• Is Part Of: European journal of immunology. Volume 45:Issue 6(2015:Jun.)
• Page Start: 1842
• Page End: 1854
• Publication Date: 2015-04-14
• Subjects: Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201445211
• Languages: English
• ISSNs: 0014-2980

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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<sup>+</sup>CD1d<sup>hi</sup> cells. Previous work has identified an expansion of these cells in mice infected with the helminth, <italic>Schistosoma mansoni</italic>. Here, microarray analysis of CD19<sup>+</sup>CD1d<sup>hi</sup> B cells from mice infected with <italic>S. mansoni</italic> demonstrated significantly increased <italic>Tlr7</italic> expression, while CD19<sup>+</sup>CD1d<sup>hi</sup> B cells from uninfected mice also demonstrated elevated <italic>Tlr7</italic> expression. Using IL‐10 reporter, <italic>Il10<sup>−/−</sup></italic> and <italic>Tlr7<sup>−/‐</sup></italic> mice, we formally demonstrate that TLR7 ligation of CD19<sup>+</sup>CD1d<sup>hi</sup> B cells increases their capacity to produce IL‐10. In a mouse model of allergic lung inflammation, the adoptive transfer of TLR7‐elicited CD19<sup>+</sup>CD1d<sup>hi</sup> B cells reduced airway inflammation and associated airway hyperresponsiveness. Using DEREG mice to deplete FoxP3<sup>+</sup> T regulatory cells in allergen‐sensitized mice, we show that that TLR7‐elicited CD19<sup>+</sup>CD1d<sup>hi</sup> 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<sup>+</sup>CD1d<sup>hi</sup> B cells, which can suppress allergic lung inflammation via T regulatory cells.</p> </abstract>