Immunological roles of intestinal mesenchymal cells

Summary The intestine is continuously exposed to an enormous variety and quantity of antigens and innate immune stimuli derived from both pathogens and harmless materials, such as food and commensal bacteria. Accordingly, the intestinal immune system is uniquely adapted to ensure appropriate responses to the different kinds of challenge; maintaining tolerance to harmless antigens in the steady‐state, whilst remaining poised to deal with potential pathogens. To accomplish this, leucocytes of the intestinal immune system have to adapt to a constantly changing environment and interact with many different non‐leucocytic intestinal cell types, including epithelial and endothelial cells, neurons, and a heterogenous network of intestinal mesenchymal cells (iMC). These interactions are intricately involved in the generation of protective immunity, the elaboration of inflammatory responses, and the development of inflammatory conditions, such as inflammatory bowel diseases. Here we discuss recent insights into the immunological functions of iMC under homeostatic and inflammatory conditions, focusing particularly on iMC in the mucosa and submucosa, and highlighting how an appreciation of the immunology of iMC may help understand the pathogenesis and treatment of disease.