BCL-6 regulates chemokine gene transcription in macrophages

Nat Immunol. 2000 Sep;1(3):214-20. doi: 10.1038/79749.

Abstract

The transcriptional repressor protein BCL-6, implicated in the pathogenesis of B cell lymphoma, regulates lymphocyte differentiation and inflammation. We investigated the mechanism for the T helper cell subset 2 (TH2)-type inflammation that occurs in BCL-6-/- mice. Using chimeric mice we found that the TH2-type inflammation is dependent upon nonlymphoid cells. We identified three chemokines, MCP-1, MCP-3 and MRP-1, which are negatively regulated by BCL-6 in macrophages. Promoter analysis revealed that BCL-6 is a potent repressor of MCP-1 transcription. Our results provide a mechanism for the regulation of TH2-type inflammation by BCL-6 and link TH2 differentiation to innate immunity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Chemokine CCL2 / biosynthesis
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / immunology
  • Chemokine CCL7
  • Chemokines / biosynthesis
  • Chemokines / genetics*
  • Chemokines / immunology
  • Chemokines, CC*
  • Cytokines*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / immunology
  • DNA-Binding Proteins / physiology*
  • Gene Expression Regulation / physiology*
  • Germinal Center / cytology
  • Germinal Center / immunology
  • Macrophages / metabolism
  • Macrophages / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Monocyte Chemoattractant Proteins / biosynthesis
  • Monocyte Chemoattractant Proteins / genetics
  • Monocyte Chemoattractant Proteins / immunology
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / immunology
  • Proto-Oncogene Proteins / physiology*
  • Proto-Oncogene Proteins c-bcl-6
  • Th2 Cells / immunology
  • Transcription Factors / genetics
  • Transcription Factors / immunology
  • Transcription Factors / physiology*
  • Transcription, Genetic / physiology*

Substances

  • Ccl7 protein, mouse
  • Chemokine CCL2
  • Chemokine CCL7
  • Chemokines
  • Chemokines, CC
  • Cytokines
  • DNA-Binding Proteins
  • Monocyte Chemoattractant Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-6
  • Transcription Factors
  • Ccl6 protein, mouse