In the gut, the immune system sets up a defensive line that is so far forward, it is on the very boundary between partly digested foods and the cells of our intestinal walls. Here, where foreign materials press against our epithelial barriers, the immune system sets up a kind of trip wire. It consists of innate lymphocytes that detect genotoxic environmental factors, including foods that wreak genetic damage inside our epithelial cells, damage that can culminate in bowel cancer.
This line of defense was recently discovered by scientists from Charité–Universitätsmedizin Berlin. According to these scientists, who were led by Andreas Diefenbach, PhD, cells of the innate immune system can detect damaging substances such as glucosinolates and, in response, release interleukin-22, a cellular messenger. The interleukin-22 signals intestinal stem cells to activate the DNA damage response (DDR).
Essentially, the DDR enables the epithelial stem cells to detect potential DNA damage earlier and repair it faster. Alternatively, the DDR can cause the cells to eliminate themselves via apoptosis rather than become cancerous.
“The immune system acts like a sensor that detects genotoxic food components,” explained Diefenbach. “Switching off this sensor results in a significant increase in cases of bowel cancer.”
Additional details about the defense mechanism appeared January 30 in the journal Nature, in an article titled, “Interleukin-22 protects intestinal stem cells against genotoxic stress.” The article describes how the cytokine interleukin-22, produced by group 3 innate lymphoid cells (ILC3) and γδ T cells, is an important regulator of the DDR machinery in intestinal epithelial stem cells.
“Using a new mouse model that enables sporadic inactivation of the IL-22 receptor in colon epithelial stem cells, we demonstrate that IL-22 is required for effective initiation of the DDR following DNA damage,” wrote the article’s authors. “Stem cells deprived of IL-22 signals and exposed to carcinogens escaped DDR-controlled apoptosis, contained more mutations and were more likely to give rise to colon cancer.”
For the immunologist, these findings are not only evidence of a previously unknown regulatory system which is used by the body to protect itself against bowel cancer. It is also evidence of the fact that the immune system’s functions are far more complex than that of a simple defense mechanism against pathogens.
“We identified metabolites of glucosinolates, a group of phytochemicals contained in cruciferous vegetables, to be a widespread source of genotoxic stress in intestinal epithelial cells,” the article continued. “These metabolites are ligands of the aryl hydrocarbon receptor (AhR), and AhR-mediated signaling in ILC3 and γδ T cells controlled their production of IL-22.”
“The immune system monitors both the healthy growth and function of different organs in the body,” noted Diefenbach. He and his team would like to use future research studies to explore the complex interaction between food components, intestinal flora, the intestinal wall, and the immune system in greater detail. “It is here,” Diefenbach asserted, “that we may find the key to why there are so many inflammatory disorders.”
