Within the body’s communication network, cells use signaling proteins called cytokines to send messages that coordinate responses, particularly within the immune system. One member of this family is Interleukin-22 (IL-22), a cytokine with a distinct method of action. Unlike many other cytokines that primarily orchestrate the behavior of immune cells, IL-22’s messages are intended for non-immune cells. This uniqueness allows it to perform a specialized set of tasks related to the body’s physical barriers.
Tissue Protection and Regeneration
The primary function of Interleukin-22 is to maintain and repair the body’s barrier tissues. Its main targets are epithelial cells, which form the protective lining of organs and surfaces exposed to the external environment, such as the skin, lungs, and the gastrointestinal tract. Receptors for IL-22 are abundantly expressed on these cells, whereas they are notably absent on immune cells, ensuring its signals are delivered precisely where needed.
When IL-22 binds to its receptor complex on an epithelial cell, it initiates a signaling cascade inside the cell, primarily through a pathway known as JAK-STAT. This activation triggers several protective programs. It encourages the cells to resist programmed cell death (apoptosis) and stimulates them to proliferate to replace any cells that have been damaged. This action of promoting cell survival and regeneration is central to healing injured tissue.
Another effect of IL-22 is its ability to bolster the chemical defenses of these barriers. The signaling it initiates induces epithelial cells to produce and secrete a variety of antimicrobial peptides. Molecules such as S100 proteins and defensins are released, which can directly attack invading pathogens. This response helps ensure that the vital barriers separating the body’s internal environment from the outside world remain intact and functional.
Production and Regulation Within the Immune System
Interleukin-22 is produced by specific populations of immune cells, acting as a messenger sent to tissues in need of support. The main sources are specialized lymphocytes, including subsets of T helper cells known as Th17 and Th22 cells, and a group of cells called innate lymphoid cells, or ILCs. These IL-22-producing cells are strategically located at barrier surfaces like the gut and skin.
The production of IL-22 is not constant; it is tightly regulated and induced by specific triggers that signal infection or tissue damage. Key activators include other cytokines, such as Interleukin-23 (IL-23) and Interleukin-1β, which are released by other immune cells when they detect microbial products or inflammatory signals. This system ensures that the tissue-protective functions of IL-22 are deployed only when required.
Regulation is further fine-tuned by a naturally occurring molecule called IL-22 binding protein (IL-22BP), which can bind to IL-22 and neutralize its activity, preventing excessive signaling. This network allows for a rapid and localized response. For instance, during the early stages of a gut infection, ILCs can quickly produce IL-22 to fortify the intestinal wall, while adaptive T cells may later provide sustained support.
IL-22’s Role in Disease
The function of Interleukin-22 can be described as a double-edged sword, as its effects can be either beneficial or detrimental depending on the disease context. In many situations, its role in promoting tissue integrity is advantageous. During certain acute infections in the gut, IL-22 is instrumental in host defense by strengthening the intestinal barrier and reducing the ability of bacteria to penetrate into the bloodstream.
Studies using models of bacterial colitis have shown that the presence of IL-22 is linked to reduced tissue damage and faster recovery. By stimulating the proliferation of epithelial cells in the intestinal lining, it helps to rapidly repair the damage caused by the infection and restore normal function. This protective role highlights the intended function of IL-22.
However, in the setting of chronic inflammation, the normally helpful actions of IL-22 can contribute to disease pathology. In autoimmune conditions like psoriasis, the sustained overproduction of IL-22 leads to the uncontrolled proliferation of skin cells, called keratinocytes. This excessive growth is a direct cause of the thickened, scaly plaques that characterize the disease.
The role of IL-22 in cancer is also complex and highly context-dependent. Its ability to promote cell survival and proliferation can be co-opted by cancer cells to fuel their own growth. In certain types of colorectal cancer, for example, higher levels of IL-22 have been associated with tumor progression.
Therapeutic Targeting of IL-22
Given its powerful and context-dependent effects, manipulating the Interleukin-22 pathway has become an area of significant interest for developing new treatments. Research is focused on two primary strategies: blocking IL-22 where it is harmful and administering it where it could be helpful.
For diseases driven by excessive IL-22 activity, such as psoriasis, the main therapeutic strategy is inhibition. This involves using drugs, typically monoclonal antibodies, that are specifically designed to block IL-22 from reaching its receptors. By neutralizing the cytokine, these treatments aim to stop the signal that drives the over-proliferation of skin cells, thereby reducing the inflammation and plaques.
Conversely, for conditions characterized by severe tissue damage, administering IL-22 is being explored as a regenerative therapy. In cases like acute graft-versus-host disease (GVHD), where the recipient’s gut lining is often severely damaged, providing recombinant IL-22 could promote healing. The goal is to leverage IL-22’s natural ability to stimulate epithelial cell survival and proliferation to repair the damaged intestinal barrier.
This therapeutic potential extends to other conditions like inflammatory bowel disease (IBD). By developing both agonists (which mimic IL-22) and antagonists (which block it), researchers hope to harness the power of this cytokine for targeted medical intervention.