High-Density-Immune-Complex Regulatory Macrophages Promote Recovery of Experimental Colitis in Mice

Macrophages not only play a fundamental role in the pathogenesis of inflammatory bowel disease (IBD), but they also play a major role in preserving intestinal homeostasis. In this work, we evaluated the role of macrophages in IBD and investigated whether the functional reprogramming of macrophages to a very specific phenotype could decrease disease pathogenesis. Thus, macrophages were stimulated in the presence of high-density immune complexes which strongly upregulate their production of IL-10 and downregulate pro-inflammatory cytokines. The transfer of these high-density-immune-complex regulatory macrophages into mice with colitis was examined as a potential therapy proposal to control the disease. Animals subjected to colitis induction received these high-density-immune-complex regulatory macrophages, and then the Disease Activity Index (DAI), and macroscopic and microscopic lesions were measured. The treated group showed a dramatic improvement in all parameters analyzed, with no difference with the control group. The colon was macroscopically normal in appearance and size, and microscopically colon architecture was preserved. The immunofluorescence migration assay showed that these cells migrated to the inflamed intestine, being able to locally produce the cytokine IL-10, which could explain the dramatic improvement in the clinical and pathological condition of the animals. Thus, our results demonstrate that the polarization of macrophages to a high IL-10 producer profile after stimulation with high-density immune complexes was decisive in controlling experimental colitis, and that macrophages are a potential therapeutic target to be explored in the control of colitis.