A Liver Tolerates A Portal Antigen by Generating Cd11c+ Cells, Which Select Fas Ligand+ Th2 Cells Via Apoptosis

Watanabe, Tomohiro; Katsukura, Hiroaki; Shirai, Yasuhiko; Yamori, Masashi; Nishi, Tatsushi; Chiba, Tsutomu; Kita, Toru; Wakatsuki, Yoshio

doi:10.1053/jhep.2003.50343

Cited by 43 publications

(57 citation statements)

References 28 publications

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“…Previous studies have shown that IL-12 not only drives Th1 differentiation but also inhibits T cell apoptosis of newly differentiated cells and thereby enhances their survival (Fuss et al, 1999;Watanabe et al, 2003). We therefore asked whether presentation of OVA peptide by PGN-stimulated NOD2-deficient APCs (CD11b + cells) to OVA-specific CD4 + T cells (OT-II T cells) affects the apoptosis of the T cells.…”

Section: Pgn-stimulated Nod2-deficient Apcs Is Associated With Decreamentioning

confidence: 97%

Nucleotide Binding Oligomerization Domain 2 Deficiency Leads to Dysregulated TLR2 Signaling and Induction of Antigen-Specific Colitis

et al. 2006

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In this study, we determined conditions leading to the development of colitis in mice with nucleotide binding oligomerization domain 2 (NOD2) deficiency, a susceptibility factor in Crohn's disease. We found that NOD2-deficient antigen-presenting cells (APCs) produced increased amounts of interleukin (IL)-12 in the presence of ovalbumin (OVA) peptide and peptidoglycan or recombinant E. coli that express OVA peptide (ECOVA). Furthermore, these APCs elicited heightened interferon-gamma (IFN-gamma) responses from cocultured OVA-specific CD4+ T cells. We then demonstrated that NOD2-deficient mice adoptively transferred OVA-specific CD4+ T cells and that administered intrarectal ECOVA developed colitis associated with the expansion of OVA-specific CD4+ T cells producing IFN-gamma. Importantly, this colitis was highly dependent on Toll-like receptor 2 (TLR2) function since it was suppressed in NOD2 and TLR2 double-deficient mice. Thus, NOD2-deficient mice become susceptible to colitis as a result of increased TLR2 responses when they have the capacity to respond to an antigen expressed by mucosal bacteria.

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Section: Pgn-stimulated Nod2-deficient Apcs Is Associated With Decreamentioning

confidence: 97%

Nucleotide Binding Oligomerization Domain 2 Deficiency Leads to Dysregulated TLR2 Signaling and Induction of Antigen-Specific Colitis

et al. 2006

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“…Given the fact that 90% of BM cells express the double mutations above, it is likely that BM-derived cells from this patient show both enhanced pro-inflammatory responses and resistance to apoptosis. To test this hypothesis, BM-derived peripheral blood monocytes were stimulated with toll-like receptor (TLR) ligands such as peptidoglycan (PGN, a TLR2 ligand), Pam 3 CSK4 (a TLR2 ligand) and lipopolysaccharide (LPS, a TLR4 ligand) to measure the percentage of apoptotic cells and the production of pro-inflammatory cytokines as described previously [12,13,14]. The percentages of annexin V + apoptotic monocytes were markedly reduced in the patient upon stimulation with PGN and LPS compared with those of the healthy control (fig.…”

Section: Case Reportmentioning

confidence: 99%

Simultaneous Occurrence of Inflammatory Bowel Disease and Myelodysplastic Syndrome due to Chromosomal Abnormalities in Bone Marrow Cells

Nakamura¹,

Watanabe²,

Hori³

et al. 2009

Digestion

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Background/Aims: Although chromosomal abnormalities in bone marrow (BM) cells, such as trisomy 8, are risk factors for the development of inflammatory bowel diseases (IBD) as well as myelodysplastic syndrome (MDS), the mechanisms of how these cytogenetic abnormalities cause intestinal inflammation are poorly understood. Methods and Results: A 55-year-old man with a 3-month history of watery diarrhea, fever and abdominal pain was admitted. Blood examinations revealed pancytopenia. Pathological analysis and endoscopic images of the entire colon led to the diagnosis of IBD of unclassified type. BM examination showed that the pancytopenia was due to MDS and that his BM cells had dual chromosomal abnormalities: 47, XY, +1, der(1;7)(q10;p10), +8. Immunological studies using peripheral blood monocytes from this patient revealed that the dual chromosomal abnormalities of BM cells led to the development of colitogenic monocytes producing a large amount of pro-inflammatory cytokines and showing resistance to apoptosis upon stimulation with microbial antigens. Conclusion: An abnormal karyotype of BM cells is not only responsible for the development of MDS, but also for IBD in this case.

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“…In addition, oral administration of Ag was found to result in massive apoptosis of Ag-specific CD4 + T cells in the liver and the emergence of T regs producing IL-4, IL-10 and TGF-b [139]. The finding that hepatic CD11c + cells that have captured ingested Ag can induce T cell apoptosis and Th2/T regs differentiation both in vitro and upon adoptive transfer suggests a critical role of liver DCs in oral tolerance induction [140]. At least four DC subsets were recently identified within the liver, including myeloid CD11c + CD8a -DCs and CD11c + CD8a + lymphoid DCs that displayed potent T cell stimulatory abilities similar to their splenic counterparts [141].…”

Section: A Role For the Liver Dcs?mentioning

confidence: 98%

Intestinal epithelial barrier and mucosal immunity

Dubois

Goubier

Joubert

et al. 2005

CMLS, Cell. Mol. Life Sci.

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Regulated mechanisms sustain the ability of the gut immune system to discriminate harmless food antigens (Ag) and commensal bacteria from pathogenic microorganisms, resulting in tolerance versus protective immunity, respectively. Antigens of the gut commensals are not simply ignored, but rather trigger an active immunosuppressive process, more commonly known as oral tolerance, which prevents the outcome of immunopathology. Both intrinsic properties of the gut microenvironment and cellular actors, as well as peripheral events induced by systemic dissemination of oral Ag, promote the induction of regulatory mechanisms that ensure maintenance of gut homeostasis. The aim of this review is to provide a synthetic update on the mechanisms of oral tolerance, with particular emphasis on the complex interplay between regulatory CD4+ T cells, dendritic cells and the gut microenvironment.

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A Liver Tolerates A Portal Antigen by Generating Cd11c+ Cells, Which Select Fas Ligand+ Th2 Cells Via Apoptosis

Abstract: Administration of an antigen (Ag) per oral route leads to apoptosis of Ag-specific CD4 ؉ T cells and to development of Th2 cells expressing Fas ligand (FasL) in the liver. We determined whether presentation of an ingested Ag in the liver alone was enough to select these

Cited by 43 publications

References 28 publications

Nucleotide Binding Oligomerization Domain 2 Deficiency Leads to Dysregulated TLR2 Signaling and Induction of Antigen-Specific Colitis

Nucleotide Binding Oligomerization Domain 2 Deficiency Leads to Dysregulated TLR2 Signaling and Induction of Antigen-Specific Colitis

Simultaneous Occurrence of Inflammatory Bowel Disease and Myelodysplastic Syndrome due to Chromosomal Abnormalities in Bone Marrow Cells

Intestinal epithelial barrier and mucosal immunity

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