Profile of interleukin-22 in gut mucosal health and disease

Figures & data

Table 1 Lymphoid cell populations able to produce IL-22

Lymphoid cells	References
CD4+ αβ T-cells (Th1, Th17, Th22)	5,14,15
CD8+ αβ T-cells (Tc22)	16
γδ T-cells	l7
NKT cells	l8
NK cells	19,20
ILC3s	14,21,22
Mast cells	23
Neutrophils	24

Abbreviations: Th, T-helper; Tc, T-cytotoxic; NKT, natural killer T-cell; ILC3s, Class 3 innate lymphoid cells; IL-22, interleukin-22.

Figure 1 IL-22 receptor structure.

Notes: Illustration of the heterodimeric IL-22 receptor (IL-22R), consisting of IL-22R1 (blue) and IL-10Rβ (purple) chains and the associated signaling molecules.
Abbreviation: IL-22, interleukin-22; MAPK, mitogen-associated protein kinase.

Table 2 IL-22 involvement in the response to pathogens

Pathogen targeted	Site of action in infected host	Reference(s)
Bacteria
Gram-negative species	Lung	37
Citrobacter rodentium	Gut	38
Mycobacterium tuberculosis	Lung	39,40
Viruses
Hepatitis B	Liver	42
Hepatitis C	Liver	41
Rotavirus	Gut	43,44
Parasites
Malaria	Liver	45
Leishmaniasis	Skin	46

Abbreviation: IL-22, interleukin-22.

Figure 2 Effects of IL-22/IL-22R signaling in gut epithelial cells.

Notes: The binding of IL-22 to its cognate receptor (IL-22R) activates a signaling cascade that can ultimately result in the induction of cell proliferation and enhancement of cell survival through induction of antiapoptotic programs, as well as in the production of antimicrobial peptides.
Abbreviation: IL-22, interleukin-22.

Figure 3 IL-22 production and regulation in the gut mucosa.

Notes: IL-22 is produced by both innate (ILC3s and γδ T-cells) and adaptive (αβ CD4+ Th17 and/or Th22 as well as CD8+ Tc17 and/or Tc22 subsets) immune cells in the gut. This occurs in response to a variety of signals, including cytokines; most importantly, IL-23 produced by DCs in response to environmental factors, including AhR ligands, dietary-derived compounds, and bacterially derived products featuring PAMPs recognized by PRR. In addition, environmental factors can also regulate IL-22 production by directly targeting IL-22-producing cell populations. Cytokines can also suppress IL-22 production directly, by antagonizing its production (TGF-β and IL-27), or indirectly, by suppressing IL-23 production (IL-25). IL-22-binding protein (IL-22BP), a soluble IL-22 receptor, binds IL-22 and prevents it from signaling its target cell populations.
Abbreviations: AhR, aryl-hydrocarbon receptor; DC, dendritic cell; IL, interleukin; PAMP, pathogen-associated molecular pattern; PRR, pattern recognition receptor; TGF-β, Transforming growth factor beta; IL-22, interleukin-22.