title: Induction of oxazolone-mediated features of atopic dermatitis in NOD-scid IL2Rγ(null) mice engrafted with human peripheral blood mononuclear cells.
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 IL2Rγ(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.
authors: Institute of Molecular Animal Breeding and Biotechnology, and Laboratory for Functional Genome Analysis, Gene Center, LMU Munich, 81377 Munich, Germany.
authors: Thomas
authors: T
authors: Nolte
authors: Maryam
authors: M
authors: Zadeh-Khorasani
authors: Orkhan
authors: O
authors: Safarov
authors: Franziska
authors: F
authors: Rueff
authors: Rita
authors: R
authors: Varga
authors: Nadja
authors: N
authors: Herbach
authors: Rüdiger
authors: R
authors: Wanke
authors: Andreas
authors: A
authors: Wollenberg
authors: Thomas
authors: T
authors: Mueller
authors: Roswitha
authors: R
authors: Gropp
authors: Eckhard
authors: E
authors: Wolf
authors: Matthias
authors: M
authors: Siebeck
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D016516:CD4-CD8 Ratio; D003876:Dermatitis, Atopic / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D053631:Interleukin Receptor Common gamma Subunit / Q000172:deficiency / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000637:transplantation*; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D010081:Oxazolone / Q000276:immunology* / Q000494:pharmacology; D012867:Skin / Q000276:immunology / Q000473:pathology; D014183:Transplantation, Heterologous
chemical_list: D000276:Adjuvants, Immunologic; C507942:Il2rg protein, mouse; D007074:Immunoglobulin G; D053631:Interleukin Receptor Common gamma Subunit; D010081:Oxazolone; D007073:Immunoglobulin E