Decreased production of interleukin‐10 and transforming growth factor‐β in Toll‐like receptor‐activated intestinal B cells in SAMP1/Yit mice

Y Mishima, S Ishihara, MM Aziz, A Oka… - …, 2010 - Wiley Online Library
Y Mishima, S Ishihara, MM Aziz, A Oka, R Kusunoki, A Otani, Y Tada, YY Li, I Moriyama…
Immunology, 2010Wiley Online Library
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 …
Summary
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‐β1 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‐β1 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‐β1 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.
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