Mucosal immune system of the GUT and ILCs
The gastrointestinal system (GIT) is the largest lymphoid tissue in the body which interfaces with the external environment. Interaction of three distinct cellular compartment shapes the biological behaviour of this system. The first cell compartment is the epithelial mesenchymal cell monolayer composed of diverse cell types and presents a physical and biological barrier against nonself components of the lumen, including pathogens and allergic molecules. The second cell compartment comprises the innate and adaptive immune system cells including mast cells, dendritic cells, ILCs, T and B cell types and humoral components like sIgA, sIgE and sIgG. The third compartment of this ecosystem is the commensal microbiota. Communication between these three different cell compartments results in either immune tolerance to antigens and commensal bacteria, or a milieu in which an inflammatory mucosal immune response can develop. Moreover, immune reactions against harmful microorganisms are also shaped by the interaction of these three cell compartments.63, 64
Luminal antigens are taken up and processed by DCs and presented to T cells leading to the development of mucosal antigen-specific immune responses such as Th1, Th2, T regulatory (Tregs), Th17 cell type or IgA-producing B cells. During homeostasis, the predominating ILC type is the ILC3s which is found mostly in the intestinal lamina propria but also in the lymphoid structures.22, 65 ILC3s are also involved in limitation of pathologic adaptive immune responses against commensal bacteria in the gut66, with a recent study demonstrating them as important producers of IL-2 in the gut, which plays a role in driving Treg cells.67
LTi cells are necessary for the development of lymphoid tissues in the fetal GIT and they can also produce cytokine IL-17.68, 69 IL-22, a cytokine produced by ILC3, can induce epithelial tight junction proteins thereby promoting epithelial barrier function70. ILC3-derived IL-22 also induces the production of antimicrobial peptides in the gut.71Moreover, experimental data have shown that in mice, ILC2s regulate intestinal eosinophil homeostasis72 and are involved in restoring the epithelial barrier function by the production of AREG (Figure 3).73 Whether human ILC2s exert similar functions is still unclear.