Detailed Analysis of Nasal Polyp Tissue Sets Stage for Future Research
NIAID Now | September 05, 2018
Credit: NIAID
A new NIAID-supported study lays the foundation for understanding the causes of and ultimately developing treatments for nasal polyps—small growths that develop on inflamed mucous membranes lining the nose and sinuses. Using state-of-the-art laboratory techniques at the single-cell level, investigators conducted the most in-depth analysis to date of human nasal polyp tissue. The work, published August 22 in Nature, opens the horizon for further research to better understand nasal polyps, as well as other diseases characterized by inflamed barrier tissues, such as asthma and eczema.
Nasal polyps are often associated with chronic rhinosinusitis—a prolonged inflammation of the nasal passages and sinuses that affects nearly 27 million people in the United States. This inflammation can cause symptoms such as chronic congestion, thick and difficult to clear secretions, and sinus pain. Severe chronic rhinosinusitis with nasal polyps is frequently linked to asthma and aspirin sensitivity.
Severe chronic rhinosinusitis is difficult to treat. While medicines may offer symptom relief, many people need surgery to improve sinus drainage and reduce blockage of the nasal passages. Unfortunately, nasal polyps often grow back following surgical removal, necessitating multiple surgeries. While some new antibody-based asthma drugs are being evaluated for treatment of nasal polyps, scientists also are working toward design of novel therapies to specifically address the condition.
To aid the development of such treatments, researchers seek to understand how the inflamed linings of the nose and sinuses function at a cellular level. In the new study, scientists at Brigham and Women’s Hospital and the Massachusetts Institute of Technology focused on the cells that make up the epithelium—the outermost layer of the mucous membrane—in the nose and sinuses. The epithelium forms a barrier separating inhaled pathogens and allergens from the tissue beneath and maintains a balance of functions that provide immune protection and the ability to clean and condition the air we inhale. A healthy epithelium comprises a diversity of specialized cell types. Some cells produce mucus to moisten and protect the barrier, some secrete antimicrobial products to fight off pathogens, and others are covered with tiny hair-like structures that help clear unwanted substances.
Using cutting-edge laboratory techniques, the researchers analyzed tissue samples collected from adults with mild to severe chronic rhinosinusitis with and without nasal polyps. Single-cell analysis allowed them to paint a detailed picture of the changes that occur in the epithelium across the spectrum of disease severity.
The researchers noted that the epithelium surrounding polyps lacks many of the specialized cells present in healthy barrier tissue. Furthermore, they found that the polyp epithelium secretes fewer antimicrobial products, reducing its capability to block infections. Additionally, the scientists identified a particular pattern of gene expression—the degree to which certain genes are turned on or off—associated with nasal polyps. They also found numerous abnormalities in polyp basal cells—stem cells that develop into specialized epithelial cells. These stem cell defects help explain the loss of specialized cells in the epithelium surrounding polyps.
Though this is early-stage research, the findings are already providing insights into the treatment of nasal polyps. For example, the scientists noted that shifts in gene expression and cell behavior were influenced by exposure of epithelial cells to IL-4 and IL-13—two cell-signaling molecules, or cytokines, associated with allergic inflammation. During the study, one participant began taking the monoclonal antibody drug dupilumab, which blocks the action of these cytokines, to treat atopic dermatitis. This allowed researchers to assess a possible effect of dupilumab, which currently is being evaluated in clinical trials as a potential chronic rhinosinusitis treatment, on sinus epithelial cells. Although expression of several genes that depend on IL-4 and IL-13 was suppressed in the patient, the researchers found that expression levels of several polyp-associated genes were not altered by the drug, suggesting that additional strategies may be needed to fully treat polyps.
This comprehensive analysis provides a wealth of information to aid the scientific community in identifying potential drug targets for future development of nasal polyp treatments. The findings also help explain how an inflammatory environment can alter the epithelium at the cellular level, which has implications for asthma and eczema research.
The work was primarily funded through NIAID’s Asthma and Allergic Diseases Cooperative Research Centers (AADCRC) program. Additional support came from the National Heart, Lung, and Blood Institute and the National Cancer Institute, both part of NIH, and from the Bill & Melinda Gates Foundation.
Reference: J Ordovas-Montanes, DF Dwyer et al. Allergic inflammatory memory in human respiratory epithelial progenitor cells. Nature DOI: 10.1038/s41586-018-0449-8 (2018).
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