A NF-κB/c-myc-dependent survival pathway is targeted by corticosteroids in immature thymocytes

Weihong Wang, Joanna Wykrzykowska, Todd Johnson, Ranjan Sen, Jyoti Sen

Research output: Contribution to journalArticle

Abstract

Glucocorticoid hormones modulate T cell maturation in vivo. While low levels of hormones are required for appropriate T cell development, high levels of glucocorticoid hormones target immature developing thymocytes for cell death during systemic stress. In this report, we propose a molecular mechanism for the induction of apoptosis in CD4+CD8+ double-positive thymocytes by dexamethasone in vivo. Dexamethasone injection induced the expression of IκBα and IκBβ in thymocytes and down-regulated NF-κB DNA binding activated by intrathymic signals. Down-regulation of NF-κB DNA binding preceded cell death, suggesting that NF-κB may be important for the survival of immature thymocytes. In addition, ex vivo treatment of thymocyte single-cell suspension with dexamethasone accelerated p65/RelA down- regulation and cell death. Conversely, NF-κB induction diminished dexamethasone-induced death. Expression of the c-myc proto-oncogene, a NF- κB target, was also reduced in thymocytes of dexamethasone-treated animals, and ectopic transgenic expression of c-myc in mice provided partial rescue of double-positive thymocytes from dexamethasone mediated cell death. These observations suggest that viability of CD4+CD8+ thymocytes may be maintained by an NF-κB/c-myc-dependent pathway in vivo.

Original languageEnglish (US)
Pages (from-to)314-322
Number of pages9
JournalJournal of Immunology
Volume162
Issue number1
StatePublished - Jan 1 1999
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology

Cite this

Wang, W., Wykrzykowska, J., Johnson, T., Sen, R., & Sen, J. (1999). A NF-κB/c-myc-dependent survival pathway is targeted by corticosteroids in immature thymocytes. Journal of Immunology, 162(1), 314-322.