Unraveling the Pathogenesis of Inflammatory Bowel Disease and Search for New Therapeutic Medicines

Abstract

The breakdown of the intestinal mucosal barrier has been shown to play a key role in the pathogenesis of intestinal immune-related disorders such as inflammatory bowel disease (IBD). IBD is a chronic inflammatory disorder with intermittent episodes of remission and relapse, and the incidence of IBD in Japan has risen dramatically in recent decades. Although sustained clinical remission has recently been recognized as an important goal of IBD therapy, there are not many treatment options to maintain long-term remission. Intestinal macrophages play pivotal roles in the regulation of immune homeostasis and inflammation in the intestine. Resident intestinal macrophages can regulate themselves and other immune cells, primarily through the spontaneous secretion of interleukin-10 (IL-10). We reported that the enhancement of IL-10 production by intestinal macrophages has the potential to be a novel therapeutic mechanism for maintaining the remission of IBD. Thus, to develop new therapeutic medicines for IBD, we screened the Wakanyaku Library derived from medicinal herbs for the ability to enhance IL-10 production by intestinal macrophages. Some compounds were identified with the potential to enhance IL-10 production by intestinal macrophages and thereby maintain long-term remission in IBD. This review focuses on our recent findings on the role of intestinal macrophages in the pathogenesis of IBD and developing a novel therapeutic strategy aimed at maintaining remission in IBD.