BCL-6 regulates chemokine gene transcription in macrophages.
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.
Toney
L M
LM
Department of Microbiology and Immunology, Walther Oncology Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Cattoretti
G
G
Graf
J A
JA
Merghoub
T
T
Pandolfi
P P
PP
Dalla-Favera
R
R
Ye
B H
BH
Dent
A L
AL
D000818:Animals; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D054410:Chemokine CCL7; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D019742:Chemokines, CC; D016207:Cytokines; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D018858:Germinal Center / Q000166:cytology / Q000276:immunology; D008264:Macrophages / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018945:Monocyte Chemoattractant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D051560:Proto-Oncogene Proteins c-bcl-6; D018418:Th2 Cells / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*
C515451:Ccl7 protein, mouse; D018932:Chemokine CCL2; D054410:Chemokine CCL7; D018925:Chemokines; D019742:Chemokines, CC; D016207:Cytokines; D004268:DNA-Binding Proteins; D018945:Monocyte Chemoattractant Proteins; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors; C070959:Ccl6 protein, mouse