- Researchers investigated how immune cells in the intestines communicate with cells of the intestinal lining and microbes in the gut.
- They found that the cells lining the intestine have a dual role in immune cell signaling and inflammation.
- They hope their findings may help in the design of new treatment strategies for autoimmune conditions like irritable bowel disease (IBD).
Trillions of microbes coexist with immune cells in the intestine. A layer of intestinal epithelial cells (IECs) acts as a first line of defense against microbes by separating them from immune cells.
Studies also show that microbiota produce metabolites such as lactate, acetate, and butyrate, which regulate IEC function.
While it is known that immune cells, IECs, and microbes communicate, whether IECs directly sense microbes or respond to other cues that occur after microbe invasion remains unknown.
Understanding more about this could help researchers develop new treatments for intestinal-related conditions.
Recently, researchers conducted several experiments to understand how intestinal immune cells detect and respond to microbes, and how they then communicate with IECs.
Dr. Sri Naveen Surapaneni, a gastroenterologist at Memorial Hermann and Texas Digestive Disease Consultants in Houston, not involved in the study, told Medical News Today that it establishes a “dual role” for IECs in both immune cell signaling and inflammation.
“Understanding the intestinal microbial homeostasis and signaling mechanisms contributing to inflammatory responses is key to combat[ing] intestinal bowel disease (IBD),” he noted.
The researchers hope their findings will lead the way for new treatments for auto-immune conditions such as IBD.
The study was published in the Journal of Experimental Medicine.
For the study, the researchers conducted several experiments on the intestines of mice. They used various imaging techniques, including
In the end, they found that immune cells in the intestines can detect microbes. These immune cells then relay signals to induce an inflammatory protein called interleukin-1 (IL-1), which
Both IL-1 and IL-22 act together on IL-1 receptors expressed on IECs activating certain genes involved with inflammation and intestinal damage.
Dr. Elizabeth R. Raskin, surgical director for the Margolis Family Inflammatory Bowel Disease (IBD) Program within the Digestive Health Institute at Hoag, not involved in the research, told MNT:
“Interestingly, when IL-1 receptors were deficient or dysfunctional in mice, they were unable to clear particular bacteria found in their intestines. On the other hand, the IL-R deficient mice were seemingly protected from developing lab-induced colitis. These findings help our understanding of the interplay between the microbiome and our intestinal cells.”
Dr. Chandrashekhar Pasare, researcher in the Division of Immunobiology and co-director of the Center for Inflammation and Tolerance at Cincinnati Children’s, one of the study authors, notes that the synergy between IL-1 R and IL-22 in generating an inflammatory response was previously unknown.
“We believe this may help explain why past treatments for IBD that focused only on inhibiting IL-1β activity had mixed results. We believe that a combined blockade of both IL-22 and IL-1R could serve as a more promising treatment for IBD,” he says.
Monoclonal antibodies that inhibit IL-22 or IL-1 receptors have already been evaluated in clinical trials for autoimmune conditions. The researchers now hope to investigate whether they could be used in combination or if developing new treatments to target the pathways simultaneously could be more effective for treating conditions like IBD.
MNT spoke with Dr. Brooks Cash, chief of gastroenterology with UTHealth Houston and Memorial Hermann, not involved in the study, about the study’s limitations. He said that as the findings come from mice, it remains to be seen whether they translate to humans, too.
“However, this is the standard and accepted pathway for discovery research and these findings deserve further attention and study with other animal models and eventually human tissue if the current observations remain consistent,” he explained.
He added that while the study raises some “important hypotheses” about possible therapeutic approaches to IBD, further studies are needed to confirm their efficacy.
“Because IL-22 is expressed in multiple organ tissues to a variable degree, it remains unclear what additional organ-specific effects or overall effects of such a dual inhibition therapeutic approach might portend,” he noted.
Dr. Surapaneni added that it remains unclear which IL family signals are responsible for the mechanisms found in the study, and that further research should focus on understanding these.
When asked about the study’s implications, Dr. Cash said:
“These findings are certainly intriguing. IL-22 has been recognized for several decades to be an important player in the regulation of inflammation. What has been less clear are the mechanisms that impact, and are impacted by, IL-22 expression and activity.”
“The current research contributes potentially important understanding to the governance of IL-22 that could lead to important therapeutic applications for patients suffering from inflammatory bowel disease and perhaps other inflammatory conditions affecting the gastrointestinal tract,” he noted.
Dr. Surapaneni added that “[s]trategies to target [or block] one or both of these IL signals may be a key for novel therapeutics to treat patients with inflammatory bowel disease.”
Finally, Dr. Raskin also noted that targeting the IL-1 receptor may halt inflammation caused by the binding of IL-1 or IL-22.