TRAIL-R as a negative regulator of innate immune cell responses

Gretchen E. Diehl, Herman H. Yue, Kristina Hsieh, Anna Kuang, Mary Ho, Lisa A. Morici, Laurel L. Lenz, Dragana Cado, Lee W. Riley, Astar Winoto

Research output: Contribution to journalArticle

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Abstract

TRAIL receptor (TRAIL-R) signaling has been implicated in inducing apoptosis in tumor cells, but little is understood about its physiological function. Here, we report the generation and characterization of TRAIL-R -/- mice, which develop normal lymphocyte populations but possess enhanced innate immune responses. TRAIL-R-/- mice exhibited increased clearance of murine cytomegalovirus that correlated with increased levels of IL-12, IFN-α, and IFN-γ. Stimulation of macrophages with Mycobacterium and Toll-like receptor (TLR)-2, -3, and -4, but not TLR9, ligands resulted in high levels of TRAIL upregulation and enhanced cytokine production in TRAIL-R-/- cells. The immediate-early TLR signaling events in TRAIL-R-/- macrophages and dendritic cells are normal, but IκB-α homeostatic regulation and NF-κB activity at later time points is perturbed. These data suggest that TRAIL-R negatively regulates innate immune responses.

Original languageEnglish (US)
Pages (from-to)877-889
Number of pages13
JournalImmunity
Volume21
Issue number6
DOIs
StatePublished - Dec 2004
Externally publishedYes

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TNF-Related Apoptosis-Inducing Ligand Receptors
Innate Immunity
Macrophages
Toll-Like Receptor 3
Muromegalovirus
Toll-Like Receptor 2
Toll-Like Receptors
Interleukin-12
Mycobacterium
Dendritic Cells
Up-Regulation
Lymphocytes
Apoptosis
Cytokines
Ligands
Population
Neoplasms

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

Diehl, G. E., Yue, H. H., Hsieh, K., Kuang, A., Ho, M., Morici, L. A., ... Winoto, A. (2004). TRAIL-R as a negative regulator of innate immune cell responses. Immunity, 21(6), 877-889. https://doi.org/10.1016/j.immuni.2004.11.008

TRAIL-R as a negative regulator of innate immune cell responses. / Diehl, Gretchen E.; Yue, Herman H.; Hsieh, Kristina; Kuang, Anna; Ho, Mary; Morici, Lisa A.; Lenz, Laurel L.; Cado, Dragana; Riley, Lee W.; Winoto, Astar.

In: Immunity, Vol. 21, No. 6, 12.2004, p. 877-889.

Research output: Contribution to journalArticle

Diehl, GE, Yue, HH, Hsieh, K, Kuang, A, Ho, M, Morici, LA, Lenz, LL, Cado, D, Riley, LW & Winoto, A 2004, 'TRAIL-R as a negative regulator of innate immune cell responses', Immunity, vol. 21, no. 6, pp. 877-889. https://doi.org/10.1016/j.immuni.2004.11.008
Diehl GE, Yue HH, Hsieh K, Kuang A, Ho M, Morici LA et al. TRAIL-R as a negative regulator of innate immune cell responses. Immunity. 2004 Dec;21(6):877-889. https://doi.org/10.1016/j.immuni.2004.11.008
Diehl, Gretchen E. ; Yue, Herman H. ; Hsieh, Kristina ; Kuang, Anna ; Ho, Mary ; Morici, Lisa A. ; Lenz, Laurel L. ; Cado, Dragana ; Riley, Lee W. ; Winoto, Astar. / TRAIL-R as a negative regulator of innate immune cell responses. In: Immunity. 2004 ; Vol. 21, No. 6. pp. 877-889.
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