TRANCE (tumor necrosis factor [TNF]-related activation-induced cytokine), a new TNF family member predominantly expressed in T cells, is a dendritic cell-specific survival factor.
TRANCE (tumor necrosis factor [TNF]-related activation-induced cytokine) is a new member of the TNF family that is induced upon T cell receptor engagement and activates c-Jun N-terminal kinase (JNK) after interaction with its putative receptor (TRANCE-R). In addition, TRANCE expression is restricted to lymphoid organs and T cells. Here, we show that high levels of TRANCE-R are detected on mature dendritic cells (DCs) but not on freshly isolated B cells, T cells, or macrophages. Signaling by TRANCE-R appears to be dependent on TNF receptor-associated factor 2 (TRAF2), since JNK induction is impaired in cells from transgenic mice overexpressing a dominant negative TRAF2 protein. TRANCE inhibits apoptosis of mouse bone marrow-derived DCs and human monocyte-derived DCs in vitro. The resulting increase in DC survival is accompanied by a proportional increase in DC-mediated T cell proliferation in a mixed leukocyte reaction. TRANCE upregulates Bcl-xL expression, suggesting a potential mechanism for enhanced DC survival. TRANCE does not induce the proliferation of or increase the survival of T or B cells. Therefore, TRANCE is a new DC-restricted survival factor that mediates T cell-DC communication and may provide a tool to selectively enhance DC activity.
Wong
B R
BR
Laboratory of Immunology, The Rockefeller University, New York 10021, USA.
Josien
R
R
Lee
S Y
SY
Sauter
B
B
Li
H L
HL
Steinman
R M
RM
Choi
Y
Y
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology; D001854:Bone Marrow Cells / Q000166:cytology; D023201:CD40 Ligand; D002352:Carrier Proteins; D002469:Cell Separation; D002470:Cell Survival; D016207:Cytokines / Q000502:physiology*; D003713:Dendritic Cells / Q000166:cytology*; D005434:Flow Cytometry; D006801:Humans; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D053245:RANK Ligand; D012333:RNA, Messenger / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B; D013601:T-Lymphocytes / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D015854:Up-Regulation; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; C494812:Bcl2l1 protein, mouse; D002352:Carrier Proteins; D016207:Cytokines; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D053245:RANK Ligand; D012333:RNA, Messenger; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D051020:bcl-X Protein; D023201:CD40 Ligand