TNF-related apoptosis-inducing ligand is involved in neutropenia of systemic lupus erythematosus

Wataru Matsuyama, Masuki Yamamoto, Ikkou Higashimoto, Ken Ichi Oonakahara, Masaki Watanabe, Kentarou Machida, Teizo Yoshimura, Nobutaka Eiraku, Masaharu Kawabata, Mitsuhiro Osame, Kimiyoshi Arimura

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63 Citations (Scopus)

Abstract

Neutropenia is a common laboratory finding in systemic lupus erythematosus (SLE). However, the molecular mechanism of SLE neutropenia has not been fully explained. In this study, we examined whether TNF-related apoptosis-inducing ligand (TRAIL) is involved in the pathogenesis of SLE neutropenia using samples from SLE patients. Serum TRAIL levels in SLE patients with neutropenia were significantly higher than those of SLE patients without neutropenia and healthy volunteers. Serum TRAIL levels showed a significant negative correlation with neutrophil counts in SLE patients. The expression of TRAIL receptor 3 was significantly lower in SLE patients with neutropenia than in patients without neutropenia or in healthy volunteers. Treatment with glucocorticoids negated the decrease of TRAIL receptor 3 expression on neutrophils of SLE patients. TRAIL may accelerate neutrophil apoptosis of neutrophils from SLE patients, and autologous T cells of SLE patients, which express TRAIL on surface, may kill autologous neutrophils. Interferon gamma and glucocorticoid modulated the expression of TRAIL on T cells of SLE patients and also modulated the expression of cellular Fas-associating protein with death domain-like interleukin-1β- converting enzyme (FLICE)-inhibitory protein (cFLIP), an inhibitor of death receptor signaling, in neutrophiis. Thus, our results provide a novel insight into the molecular pathogenesis of SLE neutropenia.

Original languageEnglish
Pages (from-to)184-191
Number of pages8
JournalBlood
Volume104
Issue number1
DOIs
Publication statusPublished - Jul 1 2004

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Matsuyama, W., Yamamoto, M., Higashimoto, I., Oonakahara, K. I., Watanabe, M., Machida, K., Yoshimura, T., Eiraku, N., Kawabata, M., Osame, M., & Arimura, K. (2004). TNF-related apoptosis-inducing ligand is involved in neutropenia of systemic lupus erythematosus. Blood, 104(1), 184-191. https://doi.org/10.1182/blood-2003-12-4274