Scientists create a cellular map to explain the mechanism for nasal infection – Xinhua

WASHINGTON, August 22 (Xinhua) – US researchers developed the first global cellular map of a human barrier tissue during inflammation, leading to a new mechanism that can explain what persistent chronic rhinosinusitis is.

The study published on Wednesday in the journal Nature offered an explanation for why some patients with sinus infection develop nasal polyps, which arise from epithelial cells that run along the airways.

The findings may also have implications for the treatment of other chronic inflammatory diseases of barrier tissues, such as asthma, eczema and inflammatory bowel disease.

Massachusetts Institute of Technology (MIT) and Brigham and Women & # 39; s Hospital researchers performed rapid RNA sequencing of thousands of individual cells in the upper airways of human patients.

"We observed large differences in gene expression in subsets of epithelial cells previously obscured in bulk tissue analyzes," said senior author Alex K. Shalek, associate professor of chemistry at MIT.

The new study has revealed that basal cells from patients with polyps have triggered a specific gene expression program that explains why those cells accumulate and form thicker layers rather than differentiate into subsets of epithelial cells necessary for the defense of the host.

This pathway seems to be directly supported by IL-4 and IL-13, two immune response cytokines known to cause allergic inflammation when overproduced at pathological levels, according to the study.

"When you look across the entire transcriptome and compare cells from patients with different disease status across thousands of genes, you can begin to understand the connections between them and discover which transcriptional programs have replaced the usual," Shalek said. The researchers also found that these basal cells retain a "memory" of their exposure to those cytokines, so this memory in stem cells can influence their subsequent patterns of gene expression and the ability to generate adult specialized epithelial cells.

The findings suggested that ongoing efforts to block the effects of IL-4 and IL-13 might be a good way to try to treat chronic rhinosinusitis, a hypothesis that the researchers validated using an antibody that has a common receptor for these two block cytokines.

The researchers analyzed the gene expression of basal cells from one of the patients with polyps before and after being treated with this antibody.

They found that most, although not all, genes that had been stimulated by IL-4 and IL-13 had returned to normal expression levels.

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