Figure 8.

The proposed mechanism of miR-155 in the pathogenesis of dextran sulfate sodium (DSS)-induced colitis. In steady state, resident macrophages maintain tolerance toward the intestinal microbiota. Upon DSS exposure, gut bacteria break through the intestinal mucosal barrier and inflammatory macrophages are recruited from blood monocytes and accumulate in the inflamed mucosa, where they produce pro-inflammatory mediators. While in the absence of miR-155, two target genes C/EBPβ and SOCS1 in Ly6C^hi monocytes are unregulated and functional. This leads to the undifferentiated M0 macrophages shifting to the M2 phenotype in a PGE2-dependent manner, with a reduced M1 gene program expression and an enhanced M2 gene program expression. The miR-155 deficiency forced M2-like dominant macrophages in lamina propria to shape the colon environment and condition the proliferation and polarization of T cells, which facilitated the maintenance of intestinal homeostasis and resolved the pathogenesis of DSS-induced colitis.