title: Decreased production of interleukin-10 and transforming growth factor-β in Toll-like receptor-activated intestinal B cells in SAMP1/Yit mice.
abstract: A unique subset of B cells expressing interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) plays an essential role in preventing inflammation and autoimmunity. We investigated the presence of this cell subset in intestines and its role in the pathogenesis of ileitis using SAMP1/Yit and age-matched control AKR/J mice. Mononuclear cells were isolated from mesenteric lymph nodes (MLNs) and the expressions of B220, CD1d, CD5, Toll-like receptor 4 (TLR4) and TLR9 in isolated cells were analysed. Purified B cells were stimulated with lipopolysaccharide (LPS) or CpG-DNA, then IL-10 and TGF-β(1) expressions were examined by enzyme immunoassay and flow cytometry. Production of IL-1β by TLR-mediated macrophages co-cultured with or without purified MLN B cells from SAMP1/Yit and AKR/J mice was evaluated. In addition, interferon-γ (IFN-γ) production in intestinal T cells co-cultured with MLN B cells were also assessed in SAMP1/Yit and AKR/J strains. The production levels of IL-10 and TGF-β(1) stimulated by LPS and CpG-DNA were significantly lower in B cells separated from MLNs from the SAMP1/Yit strain. B cells expressing IL-10 and TGF-β(1) were mainly located in a population characterized by the cell surface marker CD1d(+) . Interleukin-1β production by TLR-activated macrophages co-cultured with MLN B cells from SAMP1/Yit mice was significantly higher than that of those from AKR/J mice. Interestingly, IFN-γ production by T cells was noted only when they were co-cultured with SAMP1/Yit but not the AKR/J B cells. These results are the first to show that disorders of regulatory B-cell function under innate immune activation may cause disease pathogenesis in a murine model of Crohn's disease.
authors.affiliation: Department of Internal Medicine II, Shimane University School of Medicine, Shimane University Hospital, Shimane, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Mishima
authors.forename: Shunji
authors.initials: S
authors.lastname: Ishihara
authors.forename: Md Monowar
authors.initials: MM
authors.lastname: Aziz
authors.forename: Akihiko
authors.initials: A
authors.lastname: Oka
authors.forename: Ryusaku
authors.initials: R
authors.lastname: Kusunoki
authors.forename: Aya
authors.initials: A
authors.lastname: Otani
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Tada
authors.forename: Yong-Yu
authors.initials: YY
authors.lastname: Li
authors.forename: Ichiro
authors.initials: I
authors.lastname: Moriyama
authors.forename: Naoki
authors.initials: N
authors.lastname: Oshima
authors.forename: Takafumi
authors.initials: T
authors.lastname: Yuki
authors.forename: Yuji
authors.initials: Y
authors.lastname: Amano
authors.forename: Satoshi
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Kinoshita
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D003424:Crohn Disease / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D007079:Ileitis / Q000276:immunology / Q000378:metabolism; D007082:Ileum / Q000276:immunology / Q000378:metabolism*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000276:immunology; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008262:Macrophage Activation / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008643:Mesentery / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000276:immunology / Q000378:metabolism*; D051217:Toll-Like Receptor 9 / Q000276:immunology / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis* / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000943:Antigens, Differentiation; C408982:CPG-oligonucleotide; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D009838:Oligodeoxyribonucleotides; C493487:Tlr4 protein, mouse; C495370:Tlr9 protein, mouse; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10; D007371:Interferon-gamma