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 (T(H)2)-type inflammation that occurs in BCL-6(-/-) mice. Using chimeric mice we found t hat the T(H)2-type inflammation is dependent upon nonlymphoid cells. We ide ntified three chemokines, MCP-1, MCP-3 and MRP-1,which are negatively regul ated by BCL-6 in macrophages. Promoter analysis revealed that BCL-6 is a po tent repressor of MCP-1 transcription. Our results provide a mechanism for the regulation of T(H)2-type inflammation by BCL-6 and link TH2 differentia tion to innate immunity.