Immune Cells May Hold the Key to Inflammatory Bowel Disease Treatment

Macrophages promote healing of the intestinal epithelial barrier and can reduce inflammation in patients with inflammatory bowel disease.

Patients with inflammatory bowel disease (IBD)—including Crohn’s disease and ulcerative colitis—experience tissue damage that allows bacteria to cross the intestinal epithelial barrier and stimulate the immune system, resulting in inflammation. Repair of the epithelial barrier is crucial to reduce inflammation and normalize the intestinal environment for these patients.

Certain immune cells contain healing properties that promote tissue repair in the intestines, which may result in novel treatments for IBD, according to a study published by The Journal of Clinical Investigation.

The authors found that macrophages secrete the healing factor interleukin (IL)-10, which interacts with intestinal epithelial cells to promote healing, according to the study.

"Understanding how wounds can be healed is believed to be very important and a potential therapeutic avenue for the treatment of inflammatory bowel disease," said researcher Tim Denning, PhD. "In this study, we tried to understand some of the cellular mechanisms that are required for optimal wound healing in the intestine. To do this, we used a cutting-edge system, a colonoscope with biopsy forceps, to create a wound in mice. This is analogous to colonoscopies in humans. This cutting-edge system allowed us to begin to define what cells and factors contribute to wound healing in the mouse model."

The small intestinal wound was observed as it healed in both wild type mice and those genetically deficient in IL-10. The authors also examined the effects of IL-10 on wound healing in cell cultures.

The results suggest that macrophages are the main source of IL-10 in wounds. Additionally, IL-10 was found to stimulate in vitro intestinal wound healing and increased in expression during wound repair, according to the study.

In the cell line, IL-10 was found to enhance wound repair within 12 hours. This effect was amplified after 24 hours, according to the authors.

"Basically, you have a wound, and you have an immune cell that comes in," Dr Denning said. "That's the macrophage. The macrophage can produce a factor (IL-10), and that factor can then cause the cells that are around the wound to start closing the wound."

The investigators also found some signaling pathways the factor harnesses to commence wound repair.

IL-10 was observed to encourage intestinal wound repair by activating cAMP response element-binding protein signaling, followed by synthesis and secretion of the WNT1-inducible signaling protein 1, according to the study.

The authors noted that an increased understanding of immune cell involvement in wound repair could help develop treatments for IBD.

"The implications are that understanding these cells, the factors and the pathways may offer us the ability to modulate this pathway during inflammatory bowel disease, which could lead to treatment and promote healing and recovery from inflammatory bowel disease," Dr Denning said. "There are different ways we think about it, but perhaps we could deliver the beneficial compounds (IL-10 and the downstream signaling pathways) to those patients, orally or even intravenously, or somehow drive the natural production of those compounds."