Recently, a research team led by Professor Lei Chang from the School of Radiation Medicine and Protection at Soochow University, Professor Chunlin Shao from the Institute of Radiation Medicine at Fudan University, and Professor Lingchuan Guo from the First Affiliated Hospital of Soochow University has published a research paper titled “The SWI/SNF chromatin-remodeling subunit DPF2 regulates macrophage inflammation in intestinal injury via the CACNA1D-mediated MAPK pathway” in PNAS.
This study reveals the important role of DPF2 as a key regulator in the immune response of macrophages during intestinal injury. The absence of DPF2 enhances the regenerative capacity of the intestine after radiation-induced intestinal injury (RIII), alters the heterogeneity and polarization state of macrophages, and significantly reduces intracellular calcium levels in macrophages. Importantly, targeting DPF2 and CACNA1D in both the RIII mouse model and organoid models derived from clinical RIII patients promotes repair and proliferation.
Mechanistically, the deficiency of DPF2 leads to the loss of H3K27ac and H3K4me1 marks on the super-enhancer of CACNA1D, impairing CACNA1D mRNA expression, reducing intracellular calcium levels, and subsequently weakening MAPK signaling activity, thereby promoting the polarization of anti-inflammatory macrophages. Therefore, DPF2 and CACNA1D play crucial roles in intestinal inflammation and may serve as important therapeutic targets for alleviating RIII. These findings establish DPF2 as a key link between chromatin regulation and intestinal recovery, providing new insights into the mechanisms of intestinal repair.
The first authors of this study are Mintao Ji(Assistant Professor at the Institute of Radiation Medicine, Fudan University), Haisheng Liang (2025 Ph.D. student at the Institute of Radiation Medicine, Fudan University), and Shuai Dong(2020 master's student at the School of Radiation Medicine and Protection, Soochow University). The corresponding authors are Professor Lei Chang, Professor Chunlin Shao, and Professor Lingchuan Guo.