Intestinal immune compartmentalization: implications of tissue specific determinants in health and disease

The emerging concept of tissue specific immunity has opened the gates to new inquiries into what factors drive immune cell niche adaptation and the implications on immune homeostasis, organ specific immune diseases, and therapeutic efficacy. These issues are particularly complicated at barrier sites, which are directly exposed to an ever-changing environment. In particular, the gastrointestinal (GI) tract faces even further challenges given the profound functional and structural differences along its length, raising the possibility that it may even have to be treated as multiple organs when seeking to answer these questions. In this review, we evaluate what is known about the tissue intrinsic and extrinsic factors shaping immune compartments in the intestine. We then discuss the physiological and pathological consequences of a regionally distinct immune system in a single organ, but also discuss where our insight into the role of the compartment for disease development is still very limited. Finally, we discuss the technological and therapeutic implications this compartmentalization has. While the gut is perhaps one of the most intensely studied systems, many of these aspects apply to understanding tissue specific immunity of other organs, most notably other barrier sites such as skin, lung, and the urogenital tract.