Modulating the immune system using nasal epithelial cell culture

Modulating the immune system using nasal epithelial cell culture

According to the World Allergy Organization Journal (2014), inflammation in the nose and associated sinuses involving congestion or blockage, discharge from the nose and affected ability to smell constitutes what is termed as chronic rhinosinusitis.  While there is treatment available, irritating symptoms still persist in many patients. 4.8 days were lost per year in terms of work productivity with an annual expenditure of US $1539 per patient!

The mucosa of the nose serves as a structural barrier to toxins and microbes present in the environment. Inflammatory diseases such as chronic rhinosinusitis result when the epithelial apical junctional complex (AJC: made of cell-cell junctions) that maintains the integrity of the mucosa is affected.

Studying the mucosal cells of the respiratory system can use several systems. One example is explant models that replicate what responses to allergens or microbes occur in vivo. Yet these models can only be viable for up to only 72 hours making their use and study brief. Another challenge is the constant need for nutrients and oxygen for the tissue.

The culture of epithelial cells of the airway is homogenous and easy to culture. Yet, one needs to be careful when arriving at conclusions because these cells lack the various immune cells associated along with lacking junctions and hence barriers.

A team led by Ramezanpour reported that there is a functional and robust innate immune system in primary human nasal epithelial cells (HNECs). Additionally, these cells can be cultured to also form ciliated epithelia that form mucus and also epithelial barrier function that can be measured by Trans Epithelial Electrical Resistance (TEER). This shows the suitability of these cells to assess the immune responses and mucosal barrier to further understand inflammatory diseases, according to the 2018 published article in Scientific Reports.

Nasal brushings were collected from healthy participants and those suffering from chronic rhinitis and cultured in Bronchial Epithelial Growth Media. The culture from the patients produced more amounts of a cytokine called Interleukin-6 (IL-6) than the healthy controls when the cultures were treated with molecules that stimulate the immune system such as IFN-γ and poly (I:C) (polyinosinic-polycytidylic acid that mimics double-stranded RNA of several microbes)!

This becomes important given that the airway epithelial cells produce IL-6 when exposed to pathogens to cause inflammation!

Additionally, the responses to different treatments have been shown to be different in the epithelial cells from healthy controls and rhinitis samples suggestive of the involvement of genetics and epigenetics.

The increased activation of the cells in response to poly (I: C) becomes significant as this mimics viral nucleic acid. Viral infections are often harbingers of later and severe bacterial infections. The healthy “microbiome” of the sinus is affected by viruses that increase the chances of getting bacterial pneumonia.

Thus, cell cultures serve as important platforms to assess the immune pathways involved in chronic and inflammatory diseases such as rhinitis. This can help us design efficient systems to prevent and quickly treat the inflammation.

References:

Bachert, C., Pawankar, R., Zhang, L. et al. ICON: chronic rhinosinusitis. World Allergy Organization Journal 71–28 (2014). https://doi.org/10.1186/1939-4551-7-25

Ramezanpour, M., Bolt, H., Psaltis, A.J. et al. Primary human nasal epithelial cells: a source of poly (I:C) LMW-induced IL-6 production. Scientific Reports 811325 (2018). https://doi.org/10.1038/s41598-018-29765-0.

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