The Jmjd3-Irf4 Axis Regulates M2 Macrophage Polarization and Host Responses Against Helminth Infection

Nat Immunol. 2010 Oct;11(10):936-44. doi: 10.1038/ni.1920. Epub 2010 Aug 22.

Abstract

Polarization of macrophages to M1 or M2 cells is important for mounting responses against bacterial and helminth infections, respectively. Jumonji domain containing-3 (Jmjd3), a histone 3 Lys27 (H3K27) demethylase, has been implicated in the activation of macrophages. Here we show that Jmjd3 is essential for M2 macrophage polarization in response to helminth infection and chitin, though Jmjd3 is dispensable for M1 responses. Furthermore, Jmjd3 (also known as Kdm6b) is essential for proper bone marrow macrophage differentiation, and this function depends on demethylase activity of Jmjd3. Jmjd3 deficiency affected trimethylation of H3K27 in only a limited number of genes. Among them, we identified Irf4 as encoding a key transcription factor that controls M2 macrophage polarization. Collectively, these results show that Jmjd3-mediated H3K27 demethylation is crucial for regulating M2 macrophage development leading to anti-helminth host responses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Polarity
  • Chitin / immunology
  • Gene Expression Regulation, Enzymologic
  • Histone Demethylases / metabolism
  • Host-Parasite Interactions / immunology
  • Interferon Regulatory Factors / genetics
  • Interferon Regulatory Factors / immunology*
  • Jumonji Domain-Containing Histone Demethylases / genetics
  • Jumonji Domain-Containing Histone Demethylases / immunology*
  • Macrophage Activation / immunology*
  • Macrophages / cytology
  • Macrophages / immunology*
  • Macrophages, Alveolar / immunology*
  • Methylation
  • Mice
  • Mice, Knockout
  • Nippostrongylus / immunology*
  • Strongylida Infections / immunology*

Substances

  • Interferon Regulatory Factors
  • interferon regulatory factor-4
  • Chitin
  • Histone Demethylases
  • Jumonji Domain-Containing Histone Demethylases
  • Kdm6b protein, mouse