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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(s) -
TAKEBAYASHI KOICHI,
HOKARI RYOTA,
KURIHARA CHIE,
OKADA YOSHIKIYO,
OKUDAIRA KEISUKE,
MATSUNAGA HISAYUKI,
KOMOTO SYUNSUKE,
WATANABE CHIKAKO,
KAWAGUCHI ATSUSHI,
NAGAO SHIGEAKI,
TSUZUKI YOSHIKAZU,
MIURA SOICHIRO
Publication year - 2009
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1080/10739680802574166
Subject(s) - lipopolysaccharide , proinflammatory cytokine , lymphocyte , immune system , immunology , biology , tgf beta 1 , intravital microscopy , cell adhesion molecule , cytokine , tlr4 , transforming growth factor beta , transforming growth factor , microbiology and biotechnology , inflammation , in vivo
Objective: 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. Methods: 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. Results: 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. Conclusions: Tolerance to intraluminally administered LPS in the lymphocyte recruitment process was induced by enterobacteria, possibly via the induction of IRAK‐M and TGF‐beta.