@article{PalamidesJodeleitFoehlingeretal.2016,
  author    = {Palamides, Pia and Jodeleit, Henrika and F{\"o}hlinger, Michael and Beigel, Florian and Herbach, Nadja and Mueller, Thomas and Wolf, Eckhard and Siebeck, Matthias and Gropp, Roswitha},
  title     = {A mouse model for ulcerative colitis based on NOD-scid IL2R gamma(null) mice reconstituted with peripheral blood mononuclear cells from affected individuals},
  series = {Disease Models \& Mechanisms},
  volume    = {9},
  journal   = {Disease Models \& Mechanisms},
  doi       = {10.1242/dmm.025452},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164946},
  pages     = {985-997},
  year      = {2016},
  abstract  = {Animal models reflective of ulcerative colitis (UC) remain a major challenge, and yet are crucial to understand mechanisms underlying the onset of disease and inflammatory characteristics of relapses and remission. Mouse models in which colitis-like symptoms are induced through challenge with toxins such as oxazolone, dextran sodium sulfate (DSS) or 2,4,6-trinitrobenzenesulfonic acid (TNBS) have been instrumental in understanding the inflammatory processes of UC. However, these neither reflect the heterogeneous symptoms observed in the UC-affected population nor can they be used to test the efficacy of inhibitors developed against human targets where high sequence and structural similarity of the respective ligands is lacking. In an attempt to overcome these problems, we have developed a mouse model that relies on NOD-scid IL2R γnull mice reconstituted with peripheral blood mononuclear cells derived from UC-affected individuals. Upon challenge with ethanol, mice developed colitis-like symptoms and changes in the colon architecture, characterized by influx of inflammatory cells, edema, crypt loss, crypt abscesses and epithelial hyperplasia, as previously observed in immune-competent mice. TARC, TGFβ1 and HGF expression increased in distal parts of the colon. Analysis of human leucocytes isolated from mouse spleen revealed an increase in frequencies of CD1a+, CD64+, CD163+ and TSLPR+ CD14+ monocytes, and antigen-experienced CD44+ CD4+ and CD8+ T-cells in response to ethanol. Analysis of human leucocytes from the colon of challenged mice identified CD14+ monocytes and CD11b+ monocytes as the predominant populations. Quantitative real-time PCR (RT-PCR) analysis from distal parts of the colon indicated that IFNγ might be one of the cytokines driving inflammation. Treatment with infliximab ameliorated symptoms and pathological manifestations, whereas pitrakinra had no therapeutic benefit. Thus, this model is partially reflective of the human disease and might help to increase the translation of animal and clinical studies.},
  language  = {en}
}
@article{NolteZadehKhorasaniSafarovetal.2012,
  author    = {Nolte, Thomas and Zadeh-Khorasani, Maryam and Safarov, Orkhan and Rueff, Franziska and Varga, Rita and Herbach, Nadja and Wanke, R{\"u}diger and Wollenberg, Andreas and Mueller, Thomas and Gropp, Roswitha and Wolf, Eckhard and Siebeck, Matthias},
  title     = {Induction of oxazolone-mediated features of atopic dermatitis in NOD-scid \(IL2Rγ^{null}\) mice engrafted with human peripheral blood mononuclear cells},
  series = {Disease Models and Mechanisms},
  volume    = {6},
  journal   = {Disease Models and Mechanisms},
  doi       = {10.1242/dmm.009167},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-124150},
  pages     = {125-134},
  year      = {2012},
  abstract  = {Animal models mimicking human diseases have been used extensively to study the pathogenesis of autoimmune diseases and the efficacy of potential therapeutics. They are, however, limited with regard to their similarity to the human disease and cannot be used if the antagonist and its cognate receptor require high similarity in structure or binding. Here, we examine the induction of oxazolone-mediated features of atopic dermatitis (AD) in NOD-scid IL2Rγnull mice engrafted with human peripheral blood mononuclear cells (PBMC). The mice developed the same symptoms as immunocompetent BALB/c mice. Histological alterations induced by oxazolone were characterized by keratosis, epithelial hyperplasia and influx of inflammatory cells into the dermis and epidermis. The cellular infiltrate was identified as human leukocytes, with T cells being the major constituent. In addition, oxazolone increased human serum IgE levels. The response, however, required the engraftment of PBMC derived from patients suffering from AD, which suggests that this model reflects the immunological status of the donor. Taken together, the model described here has the potential to evaluate the efficacy of therapeutics targeting human lymphocytes in vivo and, in addition, might be developed further to elucidate molecular mechanisms inducing and sustaining flares of the disease.},
  language  = {en}
}
@article{NolteZadehKhorasaniSafarovetal.2013,
  author    = {Nolte, Thomas and Zadeh-Khorasani, Maryam and Safarov, Orkhan and Rueff, Franziska and Varga, Rita and Herbach, Nadja and Wanke, R{\"u}diger and Wollenberg, Andreas and Mueller, Thomas and Gropp, Roswitha and Wolf, Eckhard and Siebeck, Matthias},
  title     = {Induction of oxazolone-mediated features of atopic dermatitis in NOD-scid IL2R \(γ^{null}\) mice engrafted with human peripheral blood mononuclear cells},
  series = {Disease Models \& Mechanisms},
  volume    = {6},
  journal   = {Disease Models \& Mechanisms},
  doi       = {10.1242/dmm.009167},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-122189},
  pages     = {125-134},
  year      = {2013},
  abstract  = {Animal models mimicking human diseases have been used extensively to study the pathogenesis of autoimmune diseases and the efficacy of potential therapeutics. They are, however, limited with regard to their similarity to the human disease and cannot be used if the antagonist and its cognate receptor require high similarity in structure or binding. Here, we examine the induction of oxazolone-mediated features of atopic dermatitis (AD) in NOD-scid IL2R \(γ^{null}\) mice engrafted with human peripheral blood mononuclear cells (PBMC). The mice developed the same symptoms as immunocompetent BALB/c mice. Histological alterations induced by oxazolone were characterized by keratosis, epithelial hyperplasia and influx of inflammatory cells into the dermis and epidermis. The cellular infiltrate was identified as human leukocytes, with T cells being the major constituent. In addition, oxazolone increased human serum IgE levels. The response, however, required the engraftment of PBMC derived from patients suffering from AD, which suggests that this model reflects the immunological status of the donor. Taken together, the model described here has the potential to evaluate the efficacy of therapeutics targeting human lymphocytes in vivo and, in addition, might be developed further to elucidate molecular mechanisms inducing and sustaining flares of the disease.},
  language  = {en}
}