Unique imaging technique sheds light on how IBD-related cells affect intestinal tissue

New “maps” of hundreds of thousands of cells linked to inflammatory bowel disease shed more light on their effects on intestinal tissue with a newly used imaging technique called “imaging mass cytometry”. New findings from researchers at the Perelman School of Medicine at the University of Pennsylvania pave the way for better targeted and more personalized approaches to treat inflammatory bowel disease (IBD). The researchers’ work has been published in Gastroenterology.

Estimated to affect nearly seven million people worldwide, IBD is a catch-all term that covers multiple disorders involving inflammation of the gastrointestinal tract. Most cases are Crohn’s disease or ulcerative colitis, which have different clinical presentations and tend to affect the intestine in different patterns. However, there is enough overlap in symptoms that the two conditions can be difficult to tell apart.

Treatments that target specific immune signaling pathways are available for both disorders, but they do not work to the same degree for every patient and can have unwanted side effects, including an increased risk of infections.

To develop better treatments and better ways to diagnose IBD, we need to gain a more complete understanding of this set of disorders at the cellular and molecular level, and this study demonstrates a powerful new way to do it. “

Klaus Kaestner, PhD, professor of genetics, lead author of the study

Traditional pathology methods have been limited in what they can reveal in biopsied intestinal tissue from IBD patients, as they can only measure a handful of protein markers, making it difficult to distinguish all of them in detail. relevant cell types. In contrast, mass cytometry imaging uses a collection of specially designed antibodies that bind to more than 30 distinct antigens – the molecular substances that trigger the body’s immune response – allowing researchers to map all types of cells in the body. a piece of fabric given at high resolution.

Kaestner’s team, including first author Ayano Kondo, a graduate student from his lab who performed most of the analysis, applied the new imaging method to six intestinal tissue samples from Crohn’s patients and six from patients with Crohn’s. with ulcerative colitis, comparing them to samples from healthy individuals. The resulting cell maps, the first of its kind in IBD research, covered hundreds of thousands of individual cells and provided many new details about how IBD disrupts the stability of intestinal tissue. Gut epithelial cells, for example, multiplied faster in IBD tissue than in healthy tissue, and were more likely to express the immune system component HLA-DR, which may help activate an inflammatory response by immune system. These features correlated with the degree of inflammation in the two diseases.

The mapping also detailed the presence in the diseased tissue of T-reg cells; regulatory immune cells that normally help control inflammation -; and suggested that between Crohn’s disease and ulcerative colitis, there are specific differences in the patterns of other types of immune cells with which T-regs interact.

“Overall, these results give us new avenues to explore for understanding IBD, for defining patient subgroups who might benefit from more personalized treatments, and for developing new therapeutic approaches,” said Kaestner.

Source:

University of Pennsylvania

Journal reference:

Kondo, A., et al. (2021) Analysis of highly multiplexed images of sections of intestinal tissue in patients with inflammatory bowel disease. Gastroenterology. doi.org/10.1053/j.gastro.2021.08.055.

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Hector Hedgepeth

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