Ligation of TLR7 on CD19+CD1dhi B cells suppresses allergic lung inflammation via regulatory T cells |
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| Authors: | Adnan R. Khan Sylvie Amu Sean P. Saunders Emily Hams Gordon Blackshields Martin O. Leonard Casey T. Weaver Tim Sparwasser Orla Sheils Padraic G. Fallon |
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| Affiliation: | 1. Trinity Biomedical Sciences Institute, School of Medicine, Trinity College Dublin, Dublin, Ireland;2. Institute of Molecular Medicine, School of Medicine, St James's Hospital, Trinity College Dublin, Dublin, Ireland;3. Department of Histopathology, Trinity College Dublin, Sir Patrick Duns Research Laboratory, Dublin, Ireland;4. School of Medicine and Medical Sciences, The Conway Institute, University College Dublin, Belfield, Dublin, Ireland;5. Department of Pathology, University of Alabama, Birmingham, AL, USA;6. Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, a Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hanover, Germany;7. National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland |
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| 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. |
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| Keywords: | AHR Helminth IL‐10 Regulatory B cells TLR7 Treg cells |
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