The Experts below are selected from a list of 366 Experts worldwide ranked by ideXlab platform

H A Drexhage - One of the best experts on this subject based on the ideXlab platform.

  • signs of immaturity of splenic dendritic cells from the autoimmune prone BioBreeding Rat consequences for the in vitro expansion of regulator and effector t cells
    Journal of Immunology, 1999
    Co-Authors: Frans Delemarre, Peter J Simons, Hendrik Jan De Heer, H A Drexhage
    Abstract:

    From the BioBreeding-diabetic prone (BB-DP) Rat, an animal model for endocrine autoimmunity, phenotype and function of splenic dendritic cells (DC) were studied. Furthermore, the suppressive effect of peritoneal macrophages (pMφ) from the BB-DP Rat in the MLR was investigated. Lower numbers of splenic DC were isolated from BB-DP Rats than from control Wistar Rats. In the preautoimmune phase, DC of the BB-DP Rat had a lower surface MHC class II expression (and in preliminary data, a lower CD80 expression), ingested more bacteria, and had a lower stimulatory potency in the syngeneic (syn)MLR as compared with control DC. During disease development, the MHC class II expression further decreased, and a low stimulatory activity became evident in the allogeneic (allo)MLR. With regard to the expansion of suppressor/regulatory T cells, a lower percentage of RT6+ T cells but higher percentages of CD45RClow T cells were induced by BB-DP DC in synMLR, but not in alloMLR. An increase in the CD4/CD8 T cell Ratio was observed in both the syn- and alloMLR due to a relative weak expansion of CD8+ T cells with DC of the BB-DP Rat. Resident pMφ isolated from BB-DP or Wistar Rats were equally effective in suppressing the DC-driven synMLR. In conclusion, splenic DC from the BB-DP Rat have a lower accessory cell function already at young age, before the development of disease, and expanded different subsets of effector/suppressor T cells in vitro as compared with those from Wistar Rats. The dysfunction of DC from BB-DP Rats is likely to be caused by their relative immaturity as indicated by their low class II and costimulatory molecule expression and relatively high phagocytic activity.

Pieter Vanden Berghe - One of the best experts on this subject based on the ideXlab platform.

  • from intestinal permeability to dysmotility the BioBreeding Rat as a model for functional gastrointestinal disorders
    PLOS ONE, 2014
    Co-Authors: Tim Vanuytsel, Hanne Vanheel, Christophe Vanormelingen, Els Houben, Shadea Salim Rasoel, Joran Toth, Tatsuhiro Masaoka, Kristin Verbeke, Gert De Hertogh, Pieter Vanden Berghe
    Abstract:

    Background Impaired intestinal barrier function, low-grade inflammation and altered neuronal control are reported in functional gastrointestinal disorders. However, the sequence of and causal relation between these events is unclear, necessitating a spontaneous animal model. The aim of this study was to describe the natural history of intestinal permeability, mucosal and neuromuscular inflammation and nitrergic motor neuron function during the lifetime of the BioBreeding (BB) Rat. Methods Normoglycemic BB-diabetes prone (DP) and control Rats were sacrificed at different ages and jejunum was harvested to characterize intestinal permeability, inflammation and neuromuscular function. Results Both structural and functional evidence of increased intestinal permeability was found in young BB-DP Rats from the age of 50 days. In older animals, starting in the mucosa from 70 days and in half of the animals also in the muscularis propria from 110 days, an inflammatory reaction, characterized by an influx of polymorphonuclear cells and higher myeloperoxidase activity, was observed. Finally, in animals older than 110 days, coinciding with a myenteric ganglionitis, a loss of nitrergic neurons and motor function was demonstRated. Conclusion In the BB-Rat, mucosal inflammatory cell infiltRation is preceded by intestinal barrier dysfunction and followed by myenteric ganglionitis and loss of nitrergic function. This sequence supports a primary role for impaired barrier function and provides an insightful model for the pathogenesis of functional gastrointestinal disorders.

  • Gene expression analysis of inflammatory markers in BB Rats of 50–70 days expressed as fold-changes compared to the control group.
    2014
    Co-Authors: Tim Vanuytsel, Hanne Vanheel, Christophe Vanormelingen, Els Houben, Shadea Salim Rasoel, Joran Toth, Tatsuhiro Masaoka, Kristin Verbeke, Gert De Hertogh, Pieter Vanden Berghe
    Abstract:

    Data are expressed as median (interquartile range). (n = 8 animals per group at 50 days and n = 7 animals per group at 70 days).BB-DP: normoglycemic Diabetes-Prone BioBreeding Rat; IFN: Interferon; IL: Interleukin; iNOS: inducible isoform of Nitric Oxide Synthase; TNF: Tumor-Necrosis Factor.Gene expression analysis of inflammatory markers in BB Rats of 50–70 days expressed as fold-changes compared to the control group.

Lars Hornum - One of the best experts on this subject based on the ideXlab platform.

  • both gimap5 and the diabetogenic bbdp allele of gimap5 induce apoptosis in t cells
    International Immunology, 2007
    Co-Authors: Ulla Nohr Dalberg, Helle Markholst, Lars Hornum
    Abstract:

    Gimap5, a member of the GTPase of the immunity-associated protein family (Gimap), regulates T cell survival. A strong indication of this is found in the diabetes-prone BioBreeding Rat (BBDP), where a frameshift mutation in Gimap5 results in T-cell lymphopenia. We have investigated the function of human Gimap5 in T cells. We found that reduction of Gimap5 by RNA interference in Jurkat cells did not affect the number of apoptotic cells whereas transient over-expression of Gimap5 resulted in a major increase in the number of apoptotic cells. The same effect of over-expression was found in naive human T cells purified from blood but not in activated human T cells. This suggests that the apoptosis-inducing effect of Gimap5 over-expression is dependent on the activation status of the cells. Since the apoptosis-inducing effect of Gimap5 was contrary to the expected function of Gimap5 based on the phenotype of BBDP Rats, we over-expressed Rat wt Gimap5 and Gimap5 with the mutation found in BBDP (Gimap5-lyp). Both versions of Rat Gimap5 induced apoptosis when expressed in the Rat T-cell line C58(NT)D.1.G.OVAR.1, however, Gimap5-lyp greatly exacerbated cell death. Finally, we detected the subcellular localization of Gimap5 to be at the endoplasmic reticulum and by quantitative PCR, we found that endogenous Gimap5 mRNA is up-regulated in activated T cells.

  • Both Gimap5 and the diabetogenic BBDP allele of Gimap5 induce apoptosis
    2007
    Co-Authors: Ulla Nohr Dalberg, Helle Markholst, Lars Hornum
    Abstract:

    Gimap5, a member of the GTPase of the immunity-associated protein family (Gimap), regulates T cell survival. A strong indication of this is found in the diabetes-prone BioBreeding Rat (BBDP), where a frameshift mutation in Gimap5 results in T-cell lymphopenia. We have investigated the function of human Gimap5 in T cells. We found that reduction of Gimap5 by RNA interference in Jurkat cells did not affect the number of apoptotic cells whereas transient over-expression of Gimap5 resulted in a major increase in the number of apoptotic cells. The same effect of over-expression was found in naive human T cells purified from blood but not in activated human T cells. This suggests that the apoptosis-inducing effect of Gimap5 over-expression is dependent on the activation status of the cells. Since the apoptosis-inducing effect of Gimap5 was contrary to the expected function of Gimap5 based on the phenotype of BBDP Rats, we over-expressed Rat wt Gimap5 and Gimap5 with the mutation found in BBDP (Gimap5-lyp). Both versions of Rat Gimap5 induced apoptosis when expressed in the Rat T-cell line C58(NT)D.1.G.OVAR.1, however, Gimap5-lyp greatly exacerbated cell death. Finally, we detected the subcellular localization of Gimap5 to be at the endoplasmic reticulum and by quantitative PCR, we found that endogenous Gimap5 mRNA is up-regulated in activated T cells

Frans Delemarre - One of the best experts on this subject based on the ideXlab platform.

  • signs of immaturity of splenic dendritic cells from the autoimmune prone BioBreeding Rat consequences for the in vitro expansion of regulator and effector t cells
    Journal of Immunology, 1999
    Co-Authors: Frans Delemarre, Peter J Simons, Hendrik Jan De Heer, H A Drexhage
    Abstract:

    From the BioBreeding-diabetic prone (BB-DP) Rat, an animal model for endocrine autoimmunity, phenotype and function of splenic dendritic cells (DC) were studied. Furthermore, the suppressive effect of peritoneal macrophages (pMφ) from the BB-DP Rat in the MLR was investigated. Lower numbers of splenic DC were isolated from BB-DP Rats than from control Wistar Rats. In the preautoimmune phase, DC of the BB-DP Rat had a lower surface MHC class II expression (and in preliminary data, a lower CD80 expression), ingested more bacteria, and had a lower stimulatory potency in the syngeneic (syn)MLR as compared with control DC. During disease development, the MHC class II expression further decreased, and a low stimulatory activity became evident in the allogeneic (allo)MLR. With regard to the expansion of suppressor/regulatory T cells, a lower percentage of RT6+ T cells but higher percentages of CD45RClow T cells were induced by BB-DP DC in synMLR, but not in alloMLR. An increase in the CD4/CD8 T cell Ratio was observed in both the syn- and alloMLR due to a relative weak expansion of CD8+ T cells with DC of the BB-DP Rat. Resident pMφ isolated from BB-DP or Wistar Rats were equally effective in suppressing the DC-driven synMLR. In conclusion, splenic DC from the BB-DP Rat have a lower accessory cell function already at young age, before the development of disease, and expanded different subsets of effector/suppressor T cells in vitro as compared with those from Wistar Rats. The dysfunction of DC from BB-DP Rats is likely to be caused by their relative immaturity as indicated by their low class II and costimulatory molecule expression and relatively high phagocytic activity.

Tim Vanuytsel - One of the best experts on this subject based on the ideXlab platform.

  • from intestinal permeability to dysmotility the BioBreeding Rat as a model for functional gastrointestinal disorders
    PLOS ONE, 2014
    Co-Authors: Tim Vanuytsel, Hanne Vanheel, Christophe Vanormelingen, Els Houben, Shadea Salim Rasoel, Joran Toth, Tatsuhiro Masaoka, Kristin Verbeke, Gert De Hertogh, Pieter Vanden Berghe
    Abstract:

    Background Impaired intestinal barrier function, low-grade inflammation and altered neuronal control are reported in functional gastrointestinal disorders. However, the sequence of and causal relation between these events is unclear, necessitating a spontaneous animal model. The aim of this study was to describe the natural history of intestinal permeability, mucosal and neuromuscular inflammation and nitrergic motor neuron function during the lifetime of the BioBreeding (BB) Rat. Methods Normoglycemic BB-diabetes prone (DP) and control Rats were sacrificed at different ages and jejunum was harvested to characterize intestinal permeability, inflammation and neuromuscular function. Results Both structural and functional evidence of increased intestinal permeability was found in young BB-DP Rats from the age of 50 days. In older animals, starting in the mucosa from 70 days and in half of the animals also in the muscularis propria from 110 days, an inflammatory reaction, characterized by an influx of polymorphonuclear cells and higher myeloperoxidase activity, was observed. Finally, in animals older than 110 days, coinciding with a myenteric ganglionitis, a loss of nitrergic neurons and motor function was demonstRated. Conclusion In the BB-Rat, mucosal inflammatory cell infiltRation is preceded by intestinal barrier dysfunction and followed by myenteric ganglionitis and loss of nitrergic function. This sequence supports a primary role for impaired barrier function and provides an insightful model for the pathogenesis of functional gastrointestinal disorders.

  • Gene expression analysis of inflammatory markers in BB Rats of 50–70 days expressed as fold-changes compared to the control group.
    2014
    Co-Authors: Tim Vanuytsel, Hanne Vanheel, Christophe Vanormelingen, Els Houben, Shadea Salim Rasoel, Joran Toth, Tatsuhiro Masaoka, Kristin Verbeke, Gert De Hertogh, Pieter Vanden Berghe
    Abstract:

    Data are expressed as median (interquartile range). (n = 8 animals per group at 50 days and n = 7 animals per group at 70 days).BB-DP: normoglycemic Diabetes-Prone BioBreeding Rat; IFN: Interferon; IL: Interleukin; iNOS: inducible isoform of Nitric Oxide Synthase; TNF: Tumor-Necrosis Factor.Gene expression analysis of inflammatory markers in BB Rats of 50–70 days expressed as fold-changes compared to the control group.