Splenocyte apoptosis and autophagy is mediated by interferon regulatory factor 1 during murine endotoxemia

Lemeng Zhang, Jon S. Cardinal, Pinhua Pan, Brian R. Rosborough, Ying Chang, Wei Yan, Hai Huang, Timothy R. Billiar, Matthew R. Rosengart, Allan Tsung*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


Sepsis-induced lymphocyte and dendritic cell apoptosis contributes to immunosuppression, which results in an inability to eradicate the primary infection as well as a propensity to acquire new, secondary infections. Another cellular process, autophagy, is also activated in immune cells and plays a protective role. In the present study, we demonstrate that interferon regulatory factor 1 (IRF-1) regulates both immune cell apoptosis and autophagy in a murine endotoxemia model. Interferon regulatory factor 1 is activated at an early phase through a Toll-like receptor 4-dependent, myeloid differentiation primary response gene 88-independent manner in splenocytes. Furthermore, IRF-1 knockout (KO) mice are protected from a lethal endotoxemia model. This protection is associated with decreased apoptosis and increased autophagy in splenocytes. Interferon regulatory factor 1 KO mice experience decreased apoptotic cell loss, especially in CD4 + T lymphocytes and myeloid antigen-presenting cells. Meanwhile, IRF-1 KO mice demonstrate increased autophagy and improved mitochondrial integrity. This increased autophagy in KO mice is attributable, at least in part, to deactivation of mammalian target of rapamycin/P70S6 signaling-a main negative regulator of autophagy. Therefore, we propose a novel role for IRF-1 in regulating both apoptosis and autophagy in splenocytes in the setting of endotoxemia with IRF-1 promoting apoptosis and inhibiting autophagy.

Original languageEnglish
Pages (from-to)511-517
Number of pages7
Issue number5
StatePublished - May 2012
Externally publishedYes


  • Apoptosis
  • Autophagy
  • Endotoxemia
  • IRF-1
  • Splenocyte


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