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.