title: Cellular sources of pathogenic and protective TNF and experimental strategies based on utilization of TNF humanized mice.
abstract: Over the years, tumor necrosis factor (TNF) has been implicated in the pathogenesis of various inflammatory conditions and TNF antagonists are highly efficient in treatment of multiple autoimmune diseases. However, it has been shown that various cellular sources of TNF exhibit distinct and non-redundant functions that can be either deleterious or beneficial. This suggests that systemic TNF blockade, in addition to neutralization of pathogenic TNF, may abrogate its protective functions, resulting in adverse effects. Here we review the data on cellular sources of pathogenic and protective TNF and then discuss an experimental system based on humanized mice to study the role of cell-type specific TNF ablation during various disease models for development of cell-type specific TNF blockade.
authors.affiliation: German Rheumatism Research Center (DRFZ), a Leibniz Institute, Berlin 10117, Germany.
authors.forename: Caroline
authors.initials: C
authors.lastname: Winsauer
authors.affiliation: German Rheumatism Research Center (DRFZ), a Leibniz Institute, Berlin 10117, Germany; Belozersky Institute of Physico-Chemical Biology, and Biological Faculty, Lomonosov Moscow State University, Moscow 119991, Russia.
authors.forename: Andrey A
authors.initials: AA
authors.lastname: Kruglov
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, and Biological Faculty, Lomonosov Moscow State University, Moscow 119991, Russia; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia.
authors.forename: Anna A
authors.initials: AA
authors.lastname: Chashchina
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, and Biological Faculty, Lomonosov Moscow State University, Moscow 119991, Russia; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia.
authors.forename: Marina S
authors.initials: MS
authors.lastname: Drutskaya
authors.affiliation: German Rheumatism Research Center (DRFZ), a Leibniz Institute, Berlin 10117, Germany; Belozersky Institute of Physico-Chemical Biology, and Biological Faculty, Lomonosov Moscow State University, Moscow 119991, Russia; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia. Electronic address: sergei@nedos.net.
authors.forename: Sergei A
authors.initials: SA
authors.lastname: Nedospasov
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology; D051379:Mice; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology*
chemical_list: D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha
keywords: Anti-TNF therapy; Colitis; Cytokine; Humanized mice; TNF