Interleukin-25 enhances the capacity of mesenchymal stem cells to induce intestinal epithelial cell regeneration

摘要

Background: This study aimed to investigate the influence of IL-25 on the capacity of mesenchymal stem cells (MSCs) to induce intestinal epithelial cell regeneration. Methods: The CD4+IL-25R+ cells and LGR5+IL-25R+ cells in colonic mucosa of Crohn’s disease (CD) patients, ulcerative colitis (UC) patients and healthy controls were detected by immunofluorescence staining, and the CD4+IL-25R+ cells in peripheral blood were detected by flow cytometry. Rat MSCs were separated and stimulated with IL-25. Then, MSCs were further incubated in IL-25-free DMEM for 24 h, and this DMEM was collected as conditioned medium (CM). IEC-6 cells were divided into 3 groups: experimental group (CM and TNF-α), control group (DMEM and TNF-α) and negative control group (DMEM). Results: The CD4+IL-25R+ cells and LGR5+IL-25R+ cells significantly increased in the colonic mucosa of active CD patients and UC patients compared with IBD patients in remission and healthy controls. The CD4+IL-25R+ cells reduced in peripheral blood of IBD patients, which was inversely correlated with inflammatory markers (ESR and CRP). CM facilitated the migration and proliferation of IEC-6 cells in the presence of TNF-α. The protein expression of AKT, p38 and ERK increased in IEC-6 cells after treatment with CM and TNF-α. Conclusion: IL-25R is involved in Th-related mucosal inflammation and proliferation of intestinal stem cells in IBD. IL-25 enhances the capacity of MSC to induce intestinal epithelial cell regeneration, and MSC therapy with IL-25 may be a new direction for IBD treatment.