In DSS colitis, synergistic effects of mesenchymal stem-cell-derived CCL2 and CXCL12 were attributable to CCL2•CXCL12 heteromers that induced peritoneal-cavity-derived macrophage M2 polarization along with increased expression and the release of IL-10 in a CCR2- but not CXCR4-dependant manner, leading to the mitigation of intestinal inflammation. Here, CXCL12 is linked to colitis.