Pre-treatment with IL-1β enhances the efficacy of MSC transplantation in DSS-induced colitis

Mesenchymal stem cells (MSCs) have been used experimentally for treating inflammatory disorders, partly due to their immunosuppressive properties. Although interleukin-1 beta (IL-1 beta) is one of the most important inflammatory mediators, growing evidence indicates that IL-1 beta signaling elicits the immunosuppressive properties of MSCs. However, it remains unclear how IL-1 beta signaling accomplishes this activity. Here, we focus on the therapeutic efficacy of IL-1 beta-primed MSCs in the dextran sulfate sodium (DSS)-induced colitis model, in addition to the underlining mechanisms. We first found that IL-1 beta-primed MSCs, without any observable phenotype change in vitro, significantly attenuated the development of DSS-induced murine colitis. Moreover, IL-1 beta-primed MSCs modulated the balance of immune cells in the spleen and the mesenteric lymph nodes (MLNs) through elevating cyclooxygenase-2 (COX-2), IL-6 and IL-8 expression and influencing the polarization of peritoneal macrophages. Importantly, IL-1 beta-primed MSCs possessed an enhanced ability to migrate to the inflammatory site of the gut via upregulation of chemokine receptor type 4 (CXCR4) expression. In summary, IL-1 beta-primed MSCs have improved efficacy in treating DSS-induced colitis, which at least partly depends on their increased immunosuppressive capacities and enhanced migration ability. Cellular & Molecular Immunology (2012) 9, 473-481; doi:10.1038/cmi.2012.40; published online 22 October 2012