title: Ligation of TLR7 on CD19(+) CD1d(hi) B cells suppresses allergic lung inflammation via regulatory T cells.
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(+) CD1d(hi) cells. Previous work has identified an expansion of these cells in mice infected with the helminth, Schistosoma mansoni. Here, microarray analysis of CD19(+) CD1d(hi) B cells from mice infected with S. mansoni demonstrated significantly increased Tlr7 expression, while CD19(+) CD1d(hi) 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(+) CD1d(hi) B cells increases their capacity to produce IL-10. In a mouse model of allergic lung inflammation, the adoptive transfer of TLR7-elicited CD19(+) CD1d(hi) 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(+) CD1d(hi) 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(+) CD1d(hi) B cells, which can suppress allergic lung inflammation via T regulatory cells.
authors.affiliation: Trinity Biomedical Sciences Institute, School of Medicine, Trinity College Dublin, Dublin, Ireland.
authors.forename: Adnan R
authors.initials: AR
authors.lastname: Khan
authors.affiliation: Institute of Molecular Medicine, School of Medicine, St James's Hospital, Trinity College Dublin, Dublin, Ireland.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Amu
authors.affiliation: Trinity Biomedical Sciences Institute, School of Medicine, Trinity College Dublin, Dublin, Ireland.
authors.forename: Sean P
authors.initials: SP
authors.lastname: Saunders
authors.affiliation: Trinity Biomedical Sciences Institute, School of Medicine, Trinity College Dublin, Dublin, Ireland.
authors.forename: Emily
authors.initials: E
authors.lastname: Hams
authors.affiliation: Department of Histopathology, Trinity College Dublin, Sir Patrick Duns Research Laboratory, St. James's Hospital, Dublin, Ireland.
authors.forename: Gordon
authors.initials: G
authors.lastname: Blackshields
authors.affiliation: School of Medicine and Medical Sciences, The Conway Institute, University College Dublin, Belfield, Dublin, Ireland.
authors.forename: Martin O
authors.initials: MO
authors.lastname: Leonard
authors.affiliation: Department of Pathology, University of Alabama, Birmingham, AL, USA.
authors.forename: Casey T
authors.initials: CT
authors.lastname: Weaver
authors.affiliation: 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.
authors.forename: Tim
authors.initials: T
authors.lastname: Sparwasser
authors.affiliation: Department of Histopathology, Trinity College Dublin, Sir Patrick Duns Research Laboratory, St. James's Hospital, Dublin, Ireland.
authors.forename: Orla
authors.initials: O
authors.lastname: Sheils
authors.affiliation: Trinity Biomedical Sciences Institute, School of Medicine, Trinity College Dublin, Dublin, Ireland.|Institute of Molecular Medicine, School of Medicine, St James's Hospital, Trinity College Dublin, Dublin, Ireland.|National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.
authors.forename: Padraic G
authors.initials: PG
authors.lastname: Fallon
mesh_terms: D000818:Animals; D018941:Antigens, CD19 / Q000378:metabolism; D055610:Antigens, CD1d / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis; D051379:Mice; D018345:Mice, Knockout; D010047:Ovalbumin / Q000009:adverse effects; D011014:Pneumonia / Q000276:immunology* / Q000378:metabolism* / Q000469:parasitology; D011485:Protein Binding; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D012550:Schistosoma mansoni / Q000276:immunology; D012555:Schistosomiasis mansoni / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*; D051199:Toll-Like Receptor 7 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D018941:Antigens, CD19; D055610:Antigens, CD1d; D051199:Toll-Like Receptor 7; D016753:Interleukin-10; D010047:Ovalbumin
keywords: AHR; Helminth; IL-10; Regulatory B cells; TLR7 Treg cells