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

Takebayashi, Koichi; Hokari, Ryota; Kurihara, Chie; Okada, Yoshikiyo; Okudaira, Keisuke; Matsunaga, Hisayuki; Komoto, Syunsuke; Watanabe, Chikako; Kawaguchi, Atsushı; Nagao, Shigeaki; Tsuzuki, Yoshikazu; Miura, Soichiro

doi:10.1080/10739680802574166

Cited by 13 publications

(16 citation statements)

References 46 publications

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“…We have noted subtle changes in the splenic architecture of antibiotic treated infant mice, and it is clear that immune tissue organization and cellular development are disrupted when the intestinal flora is limited or corrupted [3], [7], [49], [50], [51]. GF mice have defects in mucosal and systemic lymphoid structures [52] and antibiotic treatment may also impact immune tissue structure and development due to reduced/altered expression of microbial factors that are required to induce tissue organization [53], [54]. Peripheral immune tissues (spleen and draining lymph nodes) provide a necessary scaffold to facilitate trafficking and accumulation of precursor B cells, T cells, and antigen presenting cells during the initiation of primary immune responses.…”

Section: Discussionmentioning

confidence: 99%

The Intestinal Flora Is Required to Support Antibody Responses to Systemic Immunization in Infant and Germ Free Mice

2011

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The presence of a complex and diverse intestinal flora is functionally important for regulating intestinal mucosal immune responses. However, the extent to which a balanced intestinal flora regulates systemic immune responses is still being defined. In order to specifically examine whether the acquisition of a less complex flora influences responses to immunization in the pre-weaning stages of life, we utilize a model in which infant mice acquire an intestinal flora from their mothers that has been altered by broad-spectrum antibiotics. In this model, pregnant dams are treated with a cocktail of antibiotics that alters both the density and microbial diversity of the intestinal flora. After challenge with a subcutaneous immunization, the antibiotic altered flora infant mice have lower antigen specific antibody titers compared to control age-matched mice. In a second model, we examined germ free (GF) mice to analyze how the complete lack of flora influences the ability to mount normal antibody responses following subcutaneous immunization. GF mice do not respond well to immunization and introduction of a normal flora into GF mice restores the capacity of these mice to respond. These results indicate that a gastrointestinal flora reduced in density and complexity at critical time points during development adversely impacts immune responses to systemic antigens.

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Section: Discussionmentioning

confidence: 99%

The Intestinal Flora Is Required to Support Antibody Responses to Systemic Immunization in Infant and Germ Free Mice

2011

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“…55 Inflammatory bowel disease?Lack of tolerance to commensal gastrointestinal bacteria. 49,50 Allograft tolerance?Reduced tolerance to skin allografts and reduced effectiveness of exogenous costimulatory molecule inhibition. 51 Influenza infection?Increased neutrophil recruitment to the lung and no effect on viral clearance.…”

Section: Clinical Scenarios In Which Irak-m Expression Is Beneficialmentioning

confidence: 99%

“…Takebayashi et al demonstrated that IRAK-M expression may regulate this process. 49 Intraluminal injection of LPS enhances adherence of T cells to the intestinal epithelium of germ-free mice but not specific pathogen free (SPF) mice. SPF mice show increased IRAK-M and TGF-β mRNA expression following LPS suggesting that tolerance induction is mediated by both of these molecules.…”

Section: Clinical Scenarios In Which Irak-m Expression Is Beneficialmentioning

confidence: 99%

“…SPF mice show increased IRAK-M and TGF-β mRNA expression following LPS suggesting that tolerance induction is mediated by both of these molecules. 49 Moreover, deficiencies in IRAK-M may predispose individuals to inflammatory bowel disease (IBD), as IRAK-M is on the genetic susceptibility locus for IBD. 50 In ulcerative colitis patients, an association between caspase recruitment domain (CARD15) mutant patients and IRAK-M was found, suggesting a possible impairment in the negative regulation of TLR-signaling causing IBD.…”

Section: Clinical Scenarios In Which Irak-m Expression Is Beneficialmentioning

confidence: 99%

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IRAK-M Regulation and Function in Host Defense and Immune Homeostasis

Hubbard

Moore

2010

Infectious Disease Reports

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Antigen presenting cells (APCs) of the innate immune system sense a wide range of pathogens via pattern recognition receptors (PRRs). Engagement of certain PRRs can induce production of pro-inflammatory mediators that facilitate effective clearance of pathogen. Toll-like receptors (TLRs) are a well described group of PRRs that belong to the TLR/Interleukin-1 receptor (IL-1R) superfamily. However, TLR/IL-1R induction of pro-inflammatory mediators must be regulated to prevent excessive inflammation and tissue damage. One molecule of recent interest that is known to inhibit TLR/IL-1R signaling is interleukin-1 receptor associated kinase (IRAK)-M, also known as IRAK-3. IRAK-M is expressed in a number of immune and epithelial cells types, and through its inhibition of pro-inflammatory cytokine production, IRAK-M can regulate immune homeostasis and tolerance in a number of infectious and non-infectious diseases. Furthermore, use of IRAK-M deficient animals has increased our understanding of the importance of IRAK-M in regulating immune responsiveness to a variety of pathogens. Although IRAK-M expression is typically induced through TLR signaling, IRAK-M can also be expressed in response to various endogenous and exogenous soluble factors as well as cell surface and intracellular signaling molecules.This review will focus on clinical scenarios in which expression of IRAK-M is beneficial (as in early sepsis) and those situations where IRAK-M expression is harmful to the host (as in cancer and following bone marrow transplant). There is strong rationale for therapeutic targeting of IRAK-M for clinical benefit. However, effective targeting will require a greater understanding of the transcriptional regulation of this gene.

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“…In the case of TGF-b this is of particular interest as we have found differential effects of n-3 and n-6 fatty acids and this protein is known to be involved in induction of tolerance ( 3 ) .…”

mentioning

confidence: 99%

Polyunsaturated fatty acids modify colorectal epithelial cell cytokine expression in a leucocyte co-culture model in response to probiotic bacteria

et al. 2010

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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

Abstract: Tolerance to intraluminally administered LPS in the lymphocyte recruitment process was induced by enterobacteria, possibly via the induction of IRAK-M and TGF-beta.

Cited by 13 publications

References 46 publications

The Intestinal Flora Is Required to Support Antibody Responses to Systemic Immunization in Infant and Germ Free Mice

The Intestinal Flora Is Required to Support Antibody Responses to Systemic Immunization in Infant and Germ Free Mice

IRAK-M Regulation and Function in Host Defense and Immune Homeostasis

Polyunsaturated fatty acids modify colorectal epithelial cell cytokine expression in a leucocyte co-culture model in response to probiotic bacteria

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