Figure 5. ILCs can prevent or limit chronic inflammation.

(a) In the intestine, ILC2 respond to epithelial cell-derived IL-33, IL-25 and vasoactive intestinal peptide (VIP) to promote IL-5 and IL-13-dependent recruitment of eosinophils and differentiation of alternatively activated macrophages (AAMacs). This process also occurs in the adipose tissues, however the sources of IL-25 or IL-33 are less well defined. Differentiation of AAMacs or direct stimulation of adipocytes with IL-13 or methionine-enkephalin peptides (met-enk) can promote metabolic homeostasis through a process known as beiging in the adipocytes. (b) ILC3 can limit chronic inflammation by regulating innate and adaptive immune responses in the intestine. ILC3 responses are induced in response to myeloid cell- and DC-derived IL-1β and IL-23 following recognition of pathogenic or commensal microbes. Production of ILC3-derived LTα1β2 or LTα3 can promote IgA production by B cells indirectly by modulating stromal cell or DC responses. Production of ILC3-derived GM-CSF can influence myeloid cell homeostasis to subsequently promote regulatory T cell (Treg) responses to food antigens. ILC3-intrisic MHCII can directly kill commensal bacteria-specific CD4 T cells with the potential to cause intestinal inflammation. Production of IL-22 by ILC3 can promote antimicrobial peptides by IECs to limit colonization with commensal bacteria, such as segmented filamentus bacteria (SFB), or regulate the anatomical localization of lymphoid tissue resident commensal bacteria. Further, ILC3-derived IL-22 can induce fucosylation of IECs to promote colonization with beneficial bacteria.