Twist-2 controls myeloid lineage development and function

Andrew B. Sharabi, Melissa Aldrich, Drazen Sosic, Eric N. Olson, Alan D. Friedman, Sung Hyung Lee, Si Yi Chen

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Basic helix-loop-helix (bHLH) transcription factors play critical roles in lymphoid and erythroid development; however, little is known about their role in myeloid lineage development. In this study, we identify the bHLH transcription factor Twist-2 as a key negative regulator of myeloid lineage development, as manifested by marked increases in mature myeloid populations of macrophages, neutrophils, and basophils in Twist-2-deficient mice. Mechanistic studies demonstrate that Twist-2 inhibits the proliferation as well as differentiation of granulocyte macrophage progenitors (GMP) by interacting with and inhibiting the transcription factors Runx1 and C/EBPα. Moreover, Twist-2 was found to have a contrasting effect on cytokine production: inhibiting the production of proinflammatory cytokines such as interleukin-12 (IL-12) and interferon-γ (IFNγ) while promoting the regulatory cytokine IL-10 by myeloid cells. The data from further analyses suggest that Twist-2 activates the transcription factor c-Maf, leading to IL-10 expression. In addition, Twist-2 was found to be essential for endotoxin tolerance. Thus, this study reveals the critical role of Twist-2 in regulating the development of myeloid lineages, as well as the function and inflammatory responses of mature myeloid cells.

Original languageEnglish (US)
Article numbere316
Pages (from-to)2786-2800
Number of pages15
JournalPLoS biology
Volume6
Issue number12
DOIs
StatePublished - Dec 1 2008

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ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Sharabi, A. B., Aldrich, M., Sosic, D., Olson, E. N., Friedman, A. D., Lee, S. H., & Chen, S. Y. (2008). Twist-2 controls myeloid lineage development and function. PLoS biology, 6(12), 2786-2800. [e316]. https://doi.org/10.1371/journal.pbio.0060316