title: Cutting edge: resistance to apoptosis and continuous proliferation of dendritic cells deficient for TNF receptor-1.
abstract: The individual roles of the two TNFRs on dendritic cells (DC) are poorly understood. Investigating bone marrow-derived DC from TNFR-deficient mice, we found that cultures from TNFR1(-/-) mice continue to form proliferating clusters for 6-9 mo. In contrast, DC derived from wild-type, TNFR2(-/-), or TNFR1/2(-/-) mice survived for only 3-4 wk. DC obtained from these TNFR1(-/-) long term cultures (LTC) mice show an unusual mixed immature/mature phenotype. The continuous proliferation of the LTC is GM-CSF dependent and correlates with decreased protein levels of the cyclin-dependent kinase inhibitors p27(KIP1) and p21(CIP1). Prolonged survival of TNFR1(-/-) DC appears to be independent from NF-kappaB and Bcl-2 pathways and is rather enabled by the down-regulation of CD95, resulting in the resistance to CD95 ligand-induced apoptosis. These data point to proapoptotic signals mediated via TNFR1 and antiapoptotic signals mediated via TNFR2 in DC.
authors.affiliation: Department of Dermatology, University of Erlangen, Erlangen, Germany.
authors.forename: J O
authors.initials: JO
authors.lastname: Funk
authors.forename: H
authors.initials: H
authors.lastname: Walczak
authors.forename: C
authors.initials: C
authors.lastname: Voigtländer
authors.forename: S
authors.initials: S
authors.lastname: Berchtold
authors.forename: T
authors.initials: T
authors.lastname: Baumeister
authors.forename: P
authors.initials: P
authors.lastname: Rauch
authors.forename: S
authors.initials: S
authors.lastname: Rössner
authors.forename: A
authors.initials: A
authors.lastname: Steinkasserer
authors.forename: G
authors.initials: G
authors.lastname: Schuler
authors.forename: M B
authors.initials: MB
authors.lastname: Lutz
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D017209:Apoptosis / Q000235:genetics* / Q000276:immunology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D005260:Female; D007113:Immunity, Innate / Q000235:genetics; D016130:Immunophenotyping; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018124:Receptors, Tumor Necrosis Factor / Q000172:deficiency* / Q000235:genetics*; D047888:Receptors, Tumor Necrosis Factor, Type I; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology
chemical_list: D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I