Inflammatory Bowel Disease Driven by Cytokine

The activation or suppression of inflammatory disease driven by immune cells may be contingent on the action of a certain cytokine, according to a study published by Mucosal Immunology.

More than 1.5 million Americans have inflammatory bowel disease (IBD), which is characterized by chronic inflammation of all or part of the digestive tract. Patients with Crohn’s disease and ulcerative colitis experience diarrhea, pain, fatigue, weight loss, and even death due to uncontrolled inflammation of the intestine.

Current pharmacological treatments aim to combat inflammation, while some patients must undergo surgery to remove the inflamed portion of the digestive tract, which can significantly impact quality of life.

In the study, the authors explored whether the cytokine IL-36γ, which is involved with the immune system, determines whether T cells become aggressive or suppressed during an immune response in both in vitro and in vivo models.

The authors discovered that the IL-36γ cytokine promoted the development of Th9 helper T cells, according to the study. This type of T cell is known to be involved with asthma, cancer, and inflammatory bowel disease. Additionally, they discovered that the cytokine also suppresses a beneficial type of T cell.

"We were very intrigued whether the cytokine we were studying, IL-36γ could be promoting intestinal inflammation through the development of these Th9 cells, and that's in fact what we found," said lead author Tim Denning, PhD. "When we were discovering this, we also found it simultaneously inhibits a suppressive population of T cells termed regulatory T cells or Tregs, which are known to suppress inflammatory bowel disease."

The authors believe that their findings could be used to develop novel treatments for the conditions, specifically for inflammatory bowel disease, according to the study.

"Our conclusions were that IL-36γ plays a critical role in driving the differentiation of pro-inflammatory Th9 cells and inhibiting the development of the suppressive Tregs. We think this can have major implications in the treatment of human inflammatory bowel disease, particularly ulcerative colitis, which has been shown to be associated with Th9 cells."

Previously, the authors discovered that the cytokine was highly expressed in mice and humans with inflamed intestines. Interestingly, in the prior study, the authors found that IL-36γ also was involved with the inflammatory process that aided wound healing in inflammatory bowel disease.

In the current study, the authors discovered the pro-inflammatory function of the cytokine and hypothesize that it may be modified to treat inflammatory bowel disease.

In the future, the authors plan to evaluate how to inhibit the ability of IL-36γ to bind to its receptor as a potential therapy for the condition, according to the study.

"If we can block the interaction of this cytokine with its receptor, we may be able to inhibit all of this cascade that we have defined and potentially develop a therapeutic for patients with inflammatory bowel disease, particularly ulcerative colitis," Dr Denning concluded.