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

Brian R. Wong, Régis Josien, Soo Young Lee, Birthe Sauter, Hong Li Li, Ralph M. Steinman, Yongwon Choi

Research output: Contribution to journalArticlepeer-review

738 Scopus citations

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-X(L) expression, suggesting a potential mechanism for enhanced DC survival. TRANCE does not induce the proliferation of or increase the survival oft 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.

Original languageEnglish
Pages (from-to)2075-2080
Number of pages6
JournalJournal of Experimental Medicine
Volume186
Issue number12
DOIs
StatePublished - 15 Dec 1997

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