Immunity
Chronic rhinosinusitis (CRS) is an unexpectedly common condition, affecting roughly 12 % of the global population—about one billion people. It is defined as persistent inflammation of the nasal passages and sinuses lasting more than 12 weeks, resembling a cold or sinus infection that won’t resolve.
People with CRS experience ongoing nasal congestion and facial discomfort. More than one third of these patients develop nasal polyps—soft, eosinophil‑laden growths in the nasal lining that are notoriously resistant to both surgery and medication.
Researchers at Beth Israel Deaconess Medical Center, in partnership with colleagues at Stanford Medicine, mapped the cellular mechanisms behind this condition. Their study, the largest of its kind, demonstrates for the first time how epithelial and immune cells collaborate to sustain chronic inflammation. These findings, published in Immunity, open new avenues for treating CRS and other inflammatory diseases.
“The polyp patients are the ones who really suffer,” said co‑corresponding author Sizun Jiang, Ph.D., assistant professor of medicine at BIDMC. “They get these inflammatory masses that just keep coming back no matter what we do surgically.”
To investigate why polyps recur, Jiang and the team led by Jayakar V. Nayak, MD, Ph.D., professor of Otolaryngology at Stanford, studied tissue samples from over 100 patients in North America and Asia. They applied two cutting‑edge techniques: single‑cell RNA sequencing, which profiles the activity of individual cells, and spatial transcriptomics, which maps how cells interact within their native environment.
Jiang noted that the cellular patterns uncovered in this work are not unique to the nose. “These are fundamental principles of how tissues remodel during chronic inflammation,” she said, adding that the resource will aid future research across many conditions.
The study revealed the complex cellular dialogue that drives polyp formation. “It’s like we found the cellular conspiracy behind the disease,” said lead author Guanrui Liao, MD, Ph.D., a former research fellow in Jiang’s lab.
In patients with nasal polyps, the normal repair and defense mechanisms of the epithelium are hijacked. Macrophages that usually fight infection pivot to attract eosinophils—immune cells that, while intended to combat pathogens, instead worsen inflammation in CRS. Other cells that typically regenerate healthy tissue now fuel polyp growth, and additional immune cells reinforce this vicious cycle.
The data pinpoint specific intervention points where therapies can break this loop. Moreover, the work clarifies how Dupilumab, a drug already used for CRS, targets the aberrant regenerative cells that drive polyp expansion.