Runx3 function in colon resident macrophages (RM) and CD11b+ dendritic cells (DC).

RUNX3 is one of three mammalian Runt-domain transcription factors that regulate gene expression in several types of immune cells. Runx3-deficiency in mice is associated with a multitude of defects in the adaptive and innate immunity systems, including the development of early onset colitis. Our study reveals that conditional deletion of Runx3 specifically in mononuclear phagocytes (MNP) recapitulates the early onset spontaneous colitis seen in Runx3-/- mice. We show that Runx3 is expressed in colonic MNP, including RM and the dendritic cell cDC2 subsets and its loss results in impaired differentiation/maturation of both cell types. To uncover the immuno-tolerogenic properties of Runx3 in the colon MNP we performed global transcriptional profiling employing microarrays. Colon RM and CD11b+ DC were sorted from freshly digested cecums taken from 6-8 weeks old WT and Runx3-cKO (CD11c-cre) litter mates mice. Four Runx3-cKO RM replicates were compared to 3 WT RM replicates and 3 Runx3-cKO CD11b+ DC replicates were compared to 2 WT CD11b+ DC replicates Each replicate consist a pool of 3-4 mice. RNA was extracted and hybridized to Affymetrix microarrays.