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Epigenetic regulation of dendritic cell migration

Friday, November 08, 2013 — Poster Session IV

2:00 p.m. – 4:00 p.m.

FAES Academic Center (Upper-Level Terrace)




  • T.P. Moran
  • H. Nakano
  • D.N. Cook


The chemokine receptor CCR7 is critically important for trafficking of lung DCs to lymph nodes (LN), where interaction with antigen-specific T cells results in adaptive immune responses or tolerance. We previously found that lung DCs derived from common DC precursors, but not monocytes, express CCR7 and migrate to LN. To investigate the molecular mechanisms for lineage-specific CCR7 induction, we utilized an in vitro system to generate conventional (cDCs) and monocyte-derived DCs (moDCs) from bone marrow (BM) precursors. Using Ccr7gfp reporter mice, we found that BM-derived cDCs, but not moDCs, expressed functional CCR7 following activation. The Ccr7 promoter in BM-derived cDCs was hypersensitive to DNase I, consistent with chromatin remodeling and active transcription. Chromatin immunoprecipitation studies revealed enrichment for H3K27 tri-methylation at the Ccr7 promoter in BM-derived moDCs, suggesting epigenetic regulation of CCR7 expression. Similar repressive histone modifications were also found at the Ccr7 locus in lung CD11bhiLy-6Chi moDCs, but not migratory CD103+ cDCs. Comparative gene expression analysis of lung cDCs and moDCs identified several transcription factors that potentially mediate histone modifications at the Ccr7 locus. These findings argue that lineage-specific epigenetic mechanisms regulate CCR7-dependent DC migration, and may impact the efficacy of DC-based immunotherapies.

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