Recent advances in inflammatory bowel disease: mucosal immune cells in intestinal inflammation

The intestine and its immune system have evolved to meet the extraordinary task of maintaining tolerance to the largest, most complex and diverse microbial commensal habitat, while meticulously attacking and containing even minute numbers of occasionally incoming pathogens. While our understanding is still far from complete, recent studies have provided exciting novel insights into the complex interplay of the many distinct intestinal immune cell types as well as the discovery of entirely new cell subsets. These studies have also revealed how proper development and function of the intestinal immune system is dependent on its specific microbiota, which appears to have evolutionarily co-evolved. Here we review key immune cells that maintain intestinal homeostasis and, conversely, describe how altered function and imbalances may lead to inflammatory bowel disease (IBD). We highlight the latest developments within this field, covering the major players in IBD including intestinal epithelial cells, macrophages, dendritic cells, adaptive immune cells, and the newly discovered innate lymphoid cells, which appear of characteristic importance for immune function at mucosal surfaces. We set these mucosal immune pathways in the functional context of IBD risk genes where such insight is available. Moreover, we frame our discussion of fundamental biological pathways that have been elucidated in model systems in the context of results from clinical trials in IBD that targeted key mediators secreted by these cells, as an attempt of 'functional' appraisal of these pathways in human disease.