1. Oral Tolerance Induced by Enterobacteria Altered the Process of Lymphocyte Recruitment to Intestinal Microvessels: Roles of Endothelial Cell Adhesion Molecules, TGF-beta and Negative Regulators of TLR Signaling
- Author
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Ryota Hokari, Yoshikiyo Okada, Syunsuke Komoto, Keisuke Okudaira, Koichi Takebayashi, Yoshikazu Tsuzuki, Chikako Watanabe, Chie Kurihara, Shigeaki Nagao, Soichiro Miura, Atsushi Kawaguchi, and Hisayuki Matsunaga
- Subjects
Lipopolysaccharides ,Transcriptional Activation ,Lipopolysaccharide ,Physiology ,Lymphocyte ,Biology ,Proinflammatory cytokine ,Mice ,Peritoneal cavity ,chemistry.chemical_compound ,Immune system ,Enterobacteriaceae ,Transforming Growth Factor beta ,Physiology (medical) ,TGF beta signaling pathway ,Immune Tolerance ,medicine ,Animals ,Endothelium ,Lymphocytes ,Molecular Biology ,ICAM-1 ,Cell adhesion molecule ,Toll-Like Receptors ,biochemical phenomena, metabolism, and nutrition ,Intestines ,Toll-Like Receptor 4 ,Chemotaxis, Leukocyte ,Interleukin-1 Receptor-Associated Kinases ,medicine.anatomical_structure ,chemistry ,Microvessels ,Immunology ,Cardiology and Cardiovascular Medicine ,Cell Adhesion Molecules ,Signal Transduction - Abstract
Although enterobacteria are implicated in intestinal immune response, there has been no report on how intraluminal pathogens affect lymphocyte recruitment. The aim of this study was to determine how the presence of intestinal flora affects lymphocyte migration to intestine under physiological and lipopolysaccharide (LPS)-induced inflammatory conditions.Interaction of T-cells with ileal microvessels was monitored by using an intravital microscope in mice under germ-free (GF) and specific pathogen-free (SPF) conditions. LPS was administered into either the peritoneal cavity or duodenum before lymphocyte injection.Adherence of T-cells was greater in SPF than in GF mice, indicating that the presence of enterobacteria upregulated migration under physiological conditions. Intraperitoneally administered LPS significantly increased the adherence of T-cells in both GF and SPF mice accompanied by the expression of adhesion molecules and proinflammatory cytokines. However, intraluminally administered LPS did not enhance the adherence of T-cells in SPF mice. A significant induction of increase in mRNA expression of IRAK-M, a negative regulator of TLR4 signaling, and transforming growth factor beta (TGF-beta), a regulatory cytokine, was observed in SPF mice after luminal LPS treatment.Tolerance to intraluminally administered LPS in the lymphocyte recruitment process was induced by enterobacteria, possibly via the induction of IRAK-M and TGF-beta.
- Published
- 2009