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.

巨噬细胞不仅在炎症性肠病 (IBD) 的发病机制中发挥重要作用，而且在维持肠道稳态方面也发挥着重要作用。在这项工作中，我们评估了巨噬细胞在 IBD 中的作用，并研究了巨噬细胞功能重编程为非常特定的表型是否可以减少疾病的发病机制。因此，巨噬细胞在高密度免疫复合物存在的情况下受到刺激，这些复合物强烈上调其 IL-10 的产生并下调促炎细胞因子。将这些高密度免疫复合物调节巨噬细胞转移到患有结肠炎的小鼠中，被认为是控制疾病的潜在治疗方案。接受结肠炎诱导的动物接受这些高密度免疫复合调节巨噬细胞，然后是疾病活动指数 (DAI)，并测量宏观和微观病变。治疗组在分析的所有参数中都显示出显着改善，与对照组没有差异。结肠外观和大小宏观正常，微观结肠结构保留。免疫荧光迁移试验表明，这些细胞迁移到发炎的肠道，能够在局部产生细胞因子IL-10，这可以解释动物临床和病理状况的显着改善。因此，我们的结果表明，在用高密度免疫复合物刺激后，巨噬细胞向高 IL-10 生产者分布的极化在控制实验性结肠炎中起决定性作用，并且巨噬细胞是控制结肠炎的潜在治疗靶点。