Studies reveal complex immune responses in patients receiving treatment for Crohn’s disease and ulcerative colitis
Inflammatory Bowel Disease Crohn’s disease and ulcerative colitis are long-term, incurable conditions caused by inflammation of the bowel. Both can lead to poor quality of life, increased risk of cancer, and serious complications.
In order to personalize the care of the individual, to improve the use of available treatments and above all to develop medical treatments, it is necessary to better understand the interactions between the immune system and the epithelium, the layer separating the host (ourselves) of the environment. .
Dr Polychronis Pavlidis from the School of Immunology & Microbial Sciences, in collaboration with the Nick Powell Lab at Imperial College London, recently published the results of two studies in Nature Communications and Cell Reports. The studies use human colonic organoids (3D models of the human epithelium) to map how gene expression is regulated by cytokines, key chemicals that mediate immune responses and control inflammation.
The maps allowed the researchers to identify a large overlap between different cytokines on the regulation of gene expression, as well as highlight signaling bottlenecks. By linking these maps to gene expression changes seen in inflammatory bowel disease, they were able to separate patients into groups with prognostic implications.
Unexpectedly, rather than segregating based on the type of predominant immune response, patients were grouped along an immune response complexity gradient. Patients with multiple immune responses have not benefited from advanced therapies that target only some of these responses.
The researchers were able to show that the gene expression regulated by interleukin 22, a cytokine considered to play a key role in the fight against infections and the regeneration of the epithelium, is enriched in the intestine of patients suffering from hemorrhagic rectocolitis.
Surprisingly, higher expression of these interleukin-22 regulated genes was associated with a higher risk of non-response to ustekinumab, a recently introduced advanced therapy. Using data from a large Phase 3 clinical trial and an animal model of ulcerative colitis, researchers have shown that interleukin 22 regulates the influx of neutrophils to the epithelium and contributes to inflammation and intestinal disease.
These findings add to researchers’ understanding of immune-epithelial interactions at the gut barrier, paving the way for personalized medicine approaches in inflammatory bowel disease. They are now focusing on refining their predictive tool and integrating it into care pathways that will allow a more personalized approach to patient care.
Sharing his gratitude to everyone who took part in the research, Dr Pavlidis said: