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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.

Wong BR, Josien R, Lee SY, Sauter B, Li HL, Steinman RM, Choi Y - J. Exp. Med. (1997)

Bottom Line: 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.The resulting increase in DC survival is accompanied by a proportional increase in DC-mediated T cell proliferation in a mixed leukocyte reaction.TRANCE does not induce the proliferation of or increase the survival of T or B cells.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Immunology, The Rockefeller University, New York 10021, USA.

ABSTRACT
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.

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Related in: MedlinePlus

TRANCE-R signaling is dependent on TRAF2.  Thymocytes from transgenic  mice expressing TRAF2.DN or  control littermates were stimulated with hCD8-TRANCE (1  μg/ml) on OKT8-coated (10  μg/ml) plates for the indicated  amount of time then assayed for  JNK activity. The degree of JNK  activation was analyzed on a phosphorimager (Molecular Imager  System; Bio-Rad Laboratories,  Hercules, CA) and plotted as  fold induction over time 0. Representative results of three independent experiments are shown.
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Figure 5: TRANCE-R signaling is dependent on TRAF2. Thymocytes from transgenic mice expressing TRAF2.DN or control littermates were stimulated with hCD8-TRANCE (1 μg/ml) on OKT8-coated (10 μg/ml) plates for the indicated amount of time then assayed for JNK activity. The degree of JNK activation was analyzed on a phosphorimager (Molecular Imager System; Bio-Rad Laboratories, Hercules, CA) and plotted as fold induction over time 0. Representative results of three independent experiments are shown.

Mentions: Recruitment of TRAF2 to the TNFR complex or the CD40 receptor complex is necessary for JNK activation (7–9, 23). To test the possibility that TRANCE-R also signals via TRAF2, we analyzed TRANCE-mediated JNK activation in thymocytes from transgenic mice overexpressing a dominant negative form of TRAF2 (TRAF2. DN; reference 23). JNK activity peaked 2.5-fold over unstimulated cells at 5 min in control littermates, whereas JNK induction was significantly reduced in TRAF2.DN thymocytes (Fig. 5). These results suggest that signaling from the TRANCE-R requires TRAF2. TRANCE-mediated JNK induction in DCs could not be assayed since TRAF2.DN expression has been restricted to lymphocytes in the TRAF2.DN transgenic mice. In addition, JNK activity was constitutively high in mature DCs (22), which are also known to have high levels of activated NF-κB (30), thus confounding detection of increased JNK activity.


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.

Wong BR, Josien R, Lee SY, Sauter B, Li HL, Steinman RM, Choi Y - J. Exp. Med. (1997)

TRANCE-R signaling is dependent on TRAF2.  Thymocytes from transgenic  mice expressing TRAF2.DN or  control littermates were stimulated with hCD8-TRANCE (1  μg/ml) on OKT8-coated (10  μg/ml) plates for the indicated  amount of time then assayed for  JNK activity. The degree of JNK  activation was analyzed on a phosphorimager (Molecular Imager  System; Bio-Rad Laboratories,  Hercules, CA) and plotted as  fold induction over time 0. Representative results of three independent experiments are shown.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199171&req=5

Figure 5: TRANCE-R signaling is dependent on TRAF2. Thymocytes from transgenic mice expressing TRAF2.DN or control littermates were stimulated with hCD8-TRANCE (1 μg/ml) on OKT8-coated (10 μg/ml) plates for the indicated amount of time then assayed for JNK activity. The degree of JNK activation was analyzed on a phosphorimager (Molecular Imager System; Bio-Rad Laboratories, Hercules, CA) and plotted as fold induction over time 0. Representative results of three independent experiments are shown.
Mentions: Recruitment of TRAF2 to the TNFR complex or the CD40 receptor complex is necessary for JNK activation (7–9, 23). To test the possibility that TRANCE-R also signals via TRAF2, we analyzed TRANCE-mediated JNK activation in thymocytes from transgenic mice overexpressing a dominant negative form of TRAF2 (TRAF2. DN; reference 23). JNK activity peaked 2.5-fold over unstimulated cells at 5 min in control littermates, whereas JNK induction was significantly reduced in TRAF2.DN thymocytes (Fig. 5). These results suggest that signaling from the TRANCE-R requires TRAF2. TRANCE-mediated JNK induction in DCs could not be assayed since TRAF2.DN expression has been restricted to lymphocytes in the TRAF2.DN transgenic mice. In addition, JNK activity was constitutively high in mature DCs (22), which are also known to have high levels of activated NF-κB (30), thus confounding detection of increased JNK activity.

Bottom Line: 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.The resulting increase in DC survival is accompanied by a proportional increase in DC-mediated T cell proliferation in a mixed leukocyte reaction.TRANCE does not induce the proliferation of or increase the survival of T or B cells.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Immunology, The Rockefeller University, New York 10021, USA.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus