Cancer and Inflammation Program, National Cancer Institute, NIH, Frederick, MD 21720, USA.
Sci Rep. 2020 Apr 8;10(1):6078. doi: 10.1038/s41598-020-63143-z.
Inflammation of the gastrointestinal tract contributes to the development of inflammatory bowel disease (IBD). Human IBD is modeled by administering dextran sulfate sodium (DSS) to mice. In humans and mice, inflammatory M1 macrophages contribute to the progression of IBD whereas immunosuppressive M2 macrophages protect against colitis. The TLR2/1 agonist PAM3CSK4 (PAM3) induces human and murine monocytes to differentiate into immunosuppressive M2 macrophages, suggesting that PAM3 might be of benefit in the prevention/treatment of colitis. PAM3 was therefore administered to mice treated with DSS. As hypothesized, the number of M2 macrophages rose and disease severity decreased. The critical role of M2 macrophages in this process was established by transferring purified M2 macrophages from PAM3 treated control donors into DSS recipients and reducing colitis. These findings suggest that PAM3 may represent a novel approach to the treatment of human IBD.
胃肠道炎症会导致炎症性肠病（IBD）的发生。通过给小鼠施用葡聚糖硫酸钠（DSS）来模拟人类 IBD。在人类和小鼠中，炎症性 M1 巨噬细胞有助于 IBD 的进展，而免疫抑制性 M2 巨噬细胞则可以预防结肠炎。TLR2/1 激动剂 PAM3CSK4（PAM3）可诱导人和鼠单核细胞分化为免疫抑制性 M2 巨噬细胞，提示 PAM3 可能有益于预防/治疗结肠炎。因此，给用 DSS 处理的小鼠施用 PAM3。正如假设的那样，M2 巨噬细胞的数量增加，疾病严重程度降低。通过将来自 PAM3 处理的对照供体的纯化 M2 巨噬细胞转移到 DSS 接受者中来减少结肠炎，从而证实了 M2 巨噬细胞在这一过程中的关键作用。这些发现表明，PAM3 可能代表治疗人类 IBD 的一种新方法。
