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Scientists at Weill Cornell Medicine have made a groundbreaking discovery about the immune system that could improve treatments for chronic inflammatory bowel diseases (IBD).

These conditions affect more than 2 million people in the United States, causing severe health issues and reducing the quality of life.

The immune system has many pathways to protect the body from infections.

However, sometimes these pathways become overactive, leading to autoimmune diseases like IBD, psoriasis, rheumatoid arthritis, and multiple sclerosis.

One of the immune factors involved in these diseases is interleukin-23 (IL-23). IL-23 helps fight infections but can also drive chronic inflammation, causing damage to the body.

In a study published on June 12 in Nature, researchers found that IL-23 interacts with a group of immune cells called group 3 innate lymphoid cells (ILC3s). These cells are the first line of defense in mucosal tissues like the intestines and lungs.

IL-23 activates a key regulatory factor called CTLA-4 in ILC3s, which prevents the immune system from attacking the body’s own tissues and beneficial gut bacteria. This balance is crucial for maintaining gut health but is disrupted in people with IBD.

This discovery reveals ILC3s as a critical link between IL-23-driven inflammation and immune regulation in the intestines. It also opens up new possibilities for treating cancer and managing side effects of cancer immunotherapy.

Dr. Gregory Sonnenberg, the senior author of the study, explained, “We were surprised to find this connection between two major immune pathways. Most research on CTLA-4 focused on T cells, another type of immune cell.

By showing that CTLA-4 is activated by IL-23 in ILC3s, we can now think more broadly about developing new treatments.”

Dr. Anees Ahmed, the lead author, noted that while IL-23 usually protects gut tissues, in chronic inflammatory diseases, it becomes harmful.

The researchers used single-cell RNA sequencing to study how IL-23 affects different immune cells in the healthy intestine. They found that IL-23 activates the CTLA-4 pathway in ILC3s, and blocking this pathway led to severe intestinal inflammation.

To confirm their findings in humans, the team used samples from the Jill Roberts Institute Live Cell Bank, which includes samples from both healthy individuals and IBD patients.

They found that this pathway exists in healthy intestines but is impaired in IBD patients. Dr. Robbyn Sockolow, a collaborator on the study, said this discovery might explain why IL-23 drives inflammation in IBD.

The study also suggests that this pathway could be used to fight cancer. Immunotherapy drugs that block CTLA-4 are used to boost the immune system to fight cancer. However, this can cause gut inflammation, a common side effect that forces many patients to stop treatment. The findings indicate that targeting CTLA-4 in ILC3s might help avoid this issue.

Dr. Ahmed said that more research is needed, but the goal is to develop targeted treatments that selectively block CTLA-4 or IL-23 in specific immune cells. This approach could improve cancer treatments while protecting the gut from inflammation.

Additionally, new treatments for autoimmune diseases could be developed by controlling IL-23-driven chronic inflammation without completely blocking IL-23, which is still needed to fight infections.

In summary, this research offers new insights into chronic inflammation and provides a promising path for developing better treatments for IBD, cancer, and other autoimmune diseases.

If you care about inflammation, please read studies about the big cause of inflammation in common bowel disease, and vitamin B may help fight COVID-19 and reduce inflammation.

For more health information, please see recent studies about new way to halt excessive inflammation, and results showing foods that could cause inflammation.