The Myeloid Transcription Factor KLF2 Regulates the Host Response to Polymicrobial Infection and Endotoxic Shock

Ganapati H. Mahabeleshwar, Daiji Kawanami, Nikunj Sharma, Yoichi Takami, Guangjin Zhou, Hong Shi, Lalitha Nayak, Darwin Jeyaraj, Robert Grealy, Mary White, Ross McManus, Thomas Ryan, Patrick Leahy, Zhiyong Lin, Saptarsi M. Haldar, G. Brandon Atkins, Hector R. Wong, Jerry B. Lingrel, Mukesh K. Jain

Research output: Contribution to journalArticle

80 Scopus citations

Abstract

Precise control of myeloid cell activation is required for optimal host defense. However, this activation process must be under exquisite control to prevent uncontrolled inflammation. Herein, we identify the Kruppel-like transcription factor 2 (KLF2) as a potent regulator of myeloid cell activation in vivo. Exposure of myeloid cells to hypoxia and/or bacterial products reduced KLF2 expression while inducing hypoxia inducible factor-1α (HIF-1α), findings that were recapitulated in human septic patients. Myeloid KLF2 was found to be a potent inhibitor of nuclear factor-kappaB (NF-κB)-dependent HIF-1α transcription and, consequently, a critical determinant of outcome in models of polymicrobial infection and endotoxemia. Collectively, these observations identify KLF2 as a tonic repressor of myeloid cell activation in vivo and an essential regulator of the innate immune system.

Original languageEnglish (US)
Pages (from-to)715-728
Number of pages14
JournalImmunity
Volume34
Issue number5
DOIs
StatePublished - May 27 2011
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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