Regulation of the human gut homeostasis by anti-inflammatory CD14+ CD163high CD160high myeloid cells

Abstract

The gut is a unique tissue where a refined balance is maintained between immune responses and tolerance to a variety of foreign antigens including food and commensal bacteria. Although activation of T helper (Th) cells, such as Th1 and Th17 cells, is responsible for the host defense against invading pathogens in the gut, inappropriate Th1/Th17 responses cause onset and/ or progression of inflammatory bowel disease (IBD) comprised of two major disorders; ulcerative colitis and Crohn’s disease. Therefore, the inflammatory responses by Th1/Th17 cells in the gut are tightly regulated through a number of mechanisms. In the human intestine, several innate immune cell subsets play important roles in the maintenance of the gut homeostasis by controlling adaptive immune responses. We recently identified CD14+ CD163low cells and CD14+ CD163high CD160high cells as Th17-inducing dendritic cells and anti-inflammatory phagocytes, respectively. In addition, the dysfunction of these cell subsets was observed in the patients with IBD. Therefore, it would be an important future issue to analyze the mechanisms underlying regulation of intestinal innate immune cell homeostasis for the development of a novel therapeutic intervention for IBD.