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 RAD001 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. Crohn’s disease (CD), an idiopathic inflammatory bowel disease, is characterized by a chronic intestinal immune-mediated disorder.1–4 Previous studies Carfilzomib order have
demonstrated that interference with the normal interactions between intestinal mucosal cells and microbial flora is closely associated with the pathogenesis of CD.5–7 Various susceptible genes for CD have been recently identified in several genome-wide association studies,8–12 which further implicates Protein tyrosine phosphatase their involvement in the development of CD by linking to disorders of the innate immune system. Studies focused on the innate immune system have been crucial for understanding the pathogenesis
of CD. Intestinal innate immunity is maintained by a variety of cells, including macrophages, dendritic cells, and epithelial cells, which express several pattern recognition receptors (PPRs) and can sense luminal pathogen-associated molecular patterns (PAMPs).13–17 Innate immune regulation and disorders of these cells have been widely investigated in numerous studies to elucidate the pathogenesis of CD.5–7 On the other hand, T and B lymphocytes are well recognized as antigen-specific effector immune cells that play a critical role in the adaptive immune response under physiological and pathological conditions.1,2,16–20 Although T- and B-cell-mediated adaptive immune regulation have been evaluated in great detail, the contribution of these lymphocytes in innate immune-related intestinal disorders such as CD has also been recognized. Recent studies have shown that a unique subset of B cells expressing interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) plays an essential role in preventing immune responses.21–25 This subset is currently considered to consist of regulatory B cells that designate B cells with immunoregulatory properties.