BCL6 Is Up-regulated in Th17 cells and Is Required to Repress GATA3 Activity During Th17 Differentiation (47.27)

Abstract

Abstract One important goal for immunology is a complete understanding of the regulatory mechanisms controlling the differentiation of CD4 T helper cells. The BCL6 gene, originally identified as an oncogene for B cell lymphoma, encodes a transcriptional repressor protein. We have shown previously that BCL6 is a potent inhibitor of Th2 cell differentiation, and BCL6-deficient mice develop greatly exaggerated Th2 responses and Th2-type inflammation. We have recently found that BCL6-deficient T cells are severely impaired in their ability to undergo Th17 differentiation, indicating that BCL6 function is required for normal Th17 differentiation. The cytokine IL-6 can promote Th17 differentiation, but the Th2 cytokine IL-4 strongly blocks Th17 differentiation by promoting Th2 differentiation. We have found that BCL6 is necessary to repress GATA3-mediated Th2 differentiation induced by IL-6 during Th17 differentiation. Further, we have found that BCL6 is significantly up-regulated in T cells stimulated under Th17 conditions, indicating a unique requirement for BCL6 in Th17 differentiation. These data show a novel, critical role for BCL6 in promoting Th17 responses.