Enhanced secretion of IFN-γ by activated Th1 cells occurs via reverse signaling through TNF-related activation-induced cytokine

N. J. Chen, M. W. Huang, S. L. Hsieh*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

82 Scopus citations

Abstract

Growing evidence has demonstrated that members of TNF superfamily transduce signals after engagement with their receptors. TNF-related activation-induced cytokine (TRANCE), a member of TNF superfamily, is preferentially expressed on the surface of activated CD4+ Th1 cells. The soluble receptor activator of NF-κB (RANK).Fc fusion protein suppresses IFN-γ secretion by activated Th1 cells, but does not affect IL-4 secretion by Th2 cells. The suppressive effect on IFN-γ secretion is observed when Th1 cells are activated by APCs, but not by immobilized anti-TCRβ mAb. In contrast, immobilized RANK.Fc fusion protein augments IFN-γ secretion by Th1 cells, indicating the occurrence of reverse signaling through TRANCE during T cell/APC interaction. The enhanced secretion of IFN-γ mediated via TRANCE correlates with the activation of p38 mitogen-activated protein kinase and is blocked by SB203580, a p38 mitogen-activated protein kinase-specific inhibitor. Thus, in addition to its role in activating dendritic cells by binding to the receptor RANK, TRANCE itself can signal the augmentation of IFN-γ secretion via a p38-dependent pathway, and this provides yet another example of reverse signaling by a member of TNF superfamily.

Original languageEnglish
Pages (from-to)270-276
Number of pages7
JournalJournal of Immunology
Volume166
Issue number1
DOIs
StatePublished - 1 Jan 2001

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