Fig. 2: ILC3 in maintenance of gut homeostasis and occurrence of inflammatory bowel diseases.

a Macrophages are stimulated by bacteria, releasing IL-1β. IL-1β engages an IL-1 receptor on ILC3, promoting IL-22, IL-17 and GM-CSF release. GM-CSF triggers DCs and Macrophages to generate retinoic acid and IL-10, which in turn promote the formation of Treg cells. IL-22 promotes epithelial barrier integrity and proliferation, inducing the production of AMPs, REG3γ and mucin. IL-17 can recruit neutrophils and also supports epithelial barrier protection. MHC-II-expressing ILC3 can inhibit commensal specific CD4⁺ T cells. NCR- ILC3 can switch to NCR + ILC3 with IL-1β plus IL-23 stimulation. b In IBD, the number of the IL-17-producing NCR⁻ ILC3 has been shown to be increased. IL-17 can recruit neutrophil cells. The neutrophil transmigration can disrupt junction proteins, such as E-cadherin and JAML, leading to the enhancement of epithelial permeability. The increase of the IFNγ-producing ILC1 cells of intraepithelial ILC1 and CD127⁺ ILC1 is accompanied by a large decrease in the number of NCR⁺ ILC3 cells. NCR⁺ ILC3 produces excessive IL-22 in IBD. ILC3 can differentiate into ILC1 under the stimulation of IL-12 produced by CD14⁺ DCs. This ILC3 to ILC1 plasticity is reversible in the presence of IL-23, IL-1β and retinoic acid produced by CD14⁻ DCs. The population of the IFNγ-producing ILC1 is increased at the cost of the decreased NCR⁺ ILC3 cells