Interleukin-22 in urinary tract disease - new experimental directions

Abstract

Interleukin (IL)-22 is expressed by immune cells in the urinary tract and IL-22 receptor is expressed in urothelium and renal tubule cells. IL-22 can be specifically targeted in the urinary tract or conditionally depleted in mice and targeted therapeutically in humans.

Figure 1

IL‐22 and IL‐22 receptors in the urinary tract, new tools to assess their function in vivo and emerging immunotherapies. (a) IL‐22 is produced by several immune cell subsets including group 3 innate lymphoid cells (ILC3), mucosal‐associated invariant T cells (MAIT), natural killer T cells (NKT), T helper 22 cells (Th22), γδT cells, macrophages and neutrophils. IL‐22 signals through a membrane‐bound heterodimer complex consisting of IL‐22R1 and IL‐10R2 expressed on urothelium and renal tubule epithelial cells in the bladder and kidney, respectively. The binding of IL‐22 to this membrane‐bound receptor complex activates downstream signalling pathways to induce antimicrobial, pro‐inflammatory or tissue repair/regenerative responses. IL‐22 activity is negatively regulated by the soluble high‐affinity receptor IL‐22BP. (b) Experimental mouse tools that specifically target IL‐22 receptor in the bladder and kidney epithelium, respectively. Conditional depletion of IL‐22 receptor at specific time points can be achieved by tamoxifen administration. These tools may enable future detailed mechanistic studies for multiple urinary tract disease models. (c) Emerging immunotherapies that target IL‐22 in humans.