Cutting edge: resistance to apoptosis and continuous proliferation of dendritic cells deficient for TNF receptor-1.
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.
Funk
J O
JO
Department of Dermatology, University of Erlangen, Erlangen, Germany.
Walczak
H
H
Voigtländer
C
C
Berchtold
S
S
Baumeister
T
T
Rauch
P
P
Rössner
S
S
Steinkasserer
A
A
Schuler
G
G
Lutz
M B
MB
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
D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I