RUNX3 regulates the activity of the CD11a and CD49d integrin gene promoters

The leukocyte integrins CD11a/CD18 (LFA-1, αLβ2) and CD49d (VLA-4, α4β1, α4β7) mediate leukocyte transendothelial migration during immune and inflammatory responses and provides co-stimulatory signals for the activation of T lymphocytes. Our previous studies demonstrate that the CD11a gene promoter directs CD11a/CD18 integrin expression, and it depends on two overlapping sequences within the MS7 element, RUNX-110 and CEBP-100, which are recognized by RUNX and C/EBP transcription factor families, respectively. Recognition of MS7 differs in lymphoid (RUNX) and myeloid (C/EBP and RUNX) cells and its in vivo occupancy is regulated in a competitive and differentiation-dependent manner. The functional relevance of these elements are illustrated by the fact that RUNX3 overexpression leads to enhanced CD11a/CD18 levels, whereas RUNX1-ETO-expressing cells exhibit a weak/absent CD11a/CD18 integrin cell surface expression. We now provide evidence that RUNX3 also transactivates the CD49d gene promoter, and that the increased expression of CD49d mRNA and CD49d integrins on mature monocyte-derived dendritic cells correlates with an up-regulation of RUNX3 mRNA. The regulation of CD49d and CD11a integrins by RUNX3 could potentially contribute to the enhancement of transendothelial migration, antigen presentation and T cell stimulatory capabilities of mature dendritic cells.