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.