Interleukin-4 Induced Interferon Regulatory Factor (Irf) 4 Participates in the Regulation of Alternative Macrophage Priming

Immunobiology. Sep-Oct 2010;215(9-10):821-5. doi: 10.1016/j.imbio.2010.05.031. Epub 2010 Jun 4.

Abstract

Interleukin (IL)-4 is a central regulator of T helper 2 (Th2) immune responses, and also has a major impact on innate immune cells. This cytokine primes macrophages for immune responses to parasites and induces a distinct macrophage phenotype that may also promote tissue repair. IL-4 signaling in macrophages is primarily mediated by the transcription factor signal transducer and activator of transcription 6 (Stat6), which in turn regulates a number of secondary DNA binding proteins that may participate in shaping the resulting phenotype. The impact of secondary transcription factors on IL-4-treated macrophages, however, is largely unknown. Here we show that interferon regulatory factor 4 (Irf4) is strongly induced on RNA and protein level in bone marrow-derived macrophages upon priming with IL-4. Using microarray-based whole genome expression analysis, we also demonstrate that a subset of IL-4 regulated genes, including several MHC-II genes, Ciita, Cyp1b1, and Il1rn, are dysregulated in Irf4-deficient macrophages. The presented data suggests a non-redundant role for Irf4 in shaping the phenotype of alternatively primed macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aryl Hydrocarbon Hydroxylases / genetics
  • Aryl Hydrocarbon Hydroxylases / metabolism
  • Cytochrome P-450 CYP1B1
  • Gene Expression Regulation
  • Immunity, Innate / genetics
  • Interferon Regulatory Factors / genetics
  • Interferon Regulatory Factors / immunology
  • Interferon Regulatory Factors / metabolism*
  • Interleukin 1 Receptor Antagonist Protein / genetics
  • Interleukin 1 Receptor Antagonist Protein / metabolism
  • Interleukin-4 / immunology
  • Interleukin-4 / metabolism
  • Macrophage Activation / genetics
  • Macrophages / immunology
  • Macrophages / metabolism*
  • Macrophages / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microarray Analysis
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • STAT6 Transcription Factor / genetics
  • STAT6 Transcription Factor / immunology
  • STAT6 Transcription Factor / metabolism*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism

Substances

  • Interferon Regulatory Factors
  • Interleukin 1 Receptor Antagonist Protein
  • MHC class II transactivator protein
  • Nuclear Proteins
  • STAT6 Transcription Factor
  • Trans-Activators
  • interferon regulatory factor-4
  • Interleukin-4
  • Aryl Hydrocarbon Hydroxylases
  • Cyp1b1 protein, mouse
  • Cytochrome P-450 CYP1B1