Plant homologue constitutive photomorphogenesis 9 (COP9) signalosome subunit CSN5 regulates innate immune responses in macrophages

Zhongbin Deng, Ruggero Pardi, William Cheadle, Xiaoyu Xiang, Shuangyin Zhang, Spandan V. Shah, William Grizzle, Donald Miller, John Mountz, Huang Ge Zhang

Research output: Contribution to journalArticle

Abstract

COP9 plays a role in plant innate immunity. The role of COP9 in mammalian innate immune responses is unknown. Here, we show that the COP9 signalosome subunit 5 (CSN5) is required for activation of proinflammatory kinases p38 and Erk and for down-regulation of the expression of genes regulated by nuclear factor E2-related factor 2. Mice with myeloid-specific CSN5 deficiency have lower mortality in polymicrobial sepsis. CSN5 is required for both Toll-like receptor (TLR) and reactive oxygen species-mediated deneddylation of Cul3, which is essential for Cul3/Keap1-mediated degradation of nuclear factor E2-related factor 2. On the basis of our results COP9 subunit CSN5 is considered to be an essential component of mammalian innate immunity.

Original languageEnglish
Pages (from-to)4796-4804
Number of pages9
JournalBlood
Volume117
Issue number18
DOIs
Publication statusPublished - May 5 2011

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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    Deng, Z., Pardi, R., Cheadle, W., Xiang, X., Zhang, S., Shah, S. V., Grizzle, W., Miller, D., Mountz, J., & Zhang, H. G. (2011). Plant homologue constitutive photomorphogenesis 9 (COP9) signalosome subunit CSN5 regulates innate immune responses in macrophages. Blood, 117(18), 4796-4804. https://doi.org/10.1182/blood-2010-10-314526