Unexpected Function of Rare Lung Cells in Cystic Fibrosis Unveiled by University of Iowa Researchers

In a surprising revelation, scientists from the University of Iowa have illuminated a previously undisclosed role of pulmonary ionocytes, rare lung cells. These ionocytes, found within the human lung and airway linings, have been identified as key players in the absorption of water and salt from the airway surface. This discovery challenges prior assumptions about these cells and has significant implications for understanding cystic fibrosis (CF) lung disease.

Discovery of Ionocytes in Human Lungs

Five years ago, researchers stumbled upon an unexpected revelation: ionocytes, a cell type commonly observed in fish gills and frog skin, also exist in the lining of human lungs and airways. What makes these pulmonary ionocytes particularly intriguing to CF researchers is that, despite comprising just 1% of all airway lining cells, they harbor approximately half of the total CFTR protein, the malfunctioning protein central to cystic fibrosis.

However, the precise function of these CFTR-rich ionocytes remained a puzzle until now.

CFTR Channels and Their Counterintuitive Role

The CFTR channels within airway secretory cells are known to expel chloride ions from the cell into the thin layer of liquid covering the airway surface. This airway surface liquid is crucial for defending the lungs against harmful pathogens and particles. As chloride ions exit, they promote the hydration of the airway surface due to water following the salt. Surprisingly, the latest study has revealed that CFTR channels in ionocytes act in contrast; they absorb chloride ions and facilitate moisture absorption.

Ian Thornell, Ph.D., the senior author of the study, explains, “The key feature that allows ionocytes to absorb chloride is the ionocyte-specific barttin chloride channel on the opposite membrane of the cell from the CFTR channel. Together, these two channels form a conduit for chloride through the ionocyte that helps drain the liquid lining the airways into the body.”

Implications for Cystic Fibrosis

The distinct functions of CFTR channels in these two types of airway cells—ionocytes and secretory cells—suggest that CF disease disrupts both liquid secretion and absorption processes. This revelation could have profound implications for CF lung disease and the impact of CF drugs on lung function. Current CFTR modulator therapies, which restore CFTR channel function, are likely to address both secretion and absorption processes.

In conclusion, this groundbreaking research sheds light on the unexpected role of pulmonary ionocytes in chloride absorption, challenging existing paradigms and offering valuable insights into the treatment and understanding of cystic fibrosis.

Reference: “CFTR-rich ionocytes mediate chloride absorption across airway epithelia” by Lei Lei, Soumba Traore, Guillermo S. Romano Ibarra, Philip H. Karp, Tayyab Rehman, David K. Meyerholz, Joseph Zabner, David A. Stoltz, Patrick L. Sinn, Michael J. Welsh, Paul B. McCray, and Ian M. Thornell, published in The Journal of Clinical Investigation on October 16, 2023. [DOI: 10.1172/JCI171268]

The research team from the University of Iowa, including co-senior author Paul McCray Jr., MD, and study first author Lei Lei, PhD, along with other contributing researchers, played a pivotal role in this research. Funding for the study was provided in part by grants from the National Institutes of Health (DK054759, HL09184, HL133089, HL147366, and HL152960) and the Cystic Fibrosis Foundation.

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More about Cystic Fibrosis Lung Cells

• The Journal of Clinical Investigation: The official publication where the research on pulmonary ionocytes and chloride absorption was published.
• University of Iowa: The institution where the research was conducted, with potential additional information about the study.
• Cystic Fibrosis Foundation: Mentioned as a source of funding for the research, this organization may provide insights into cystic fibrosis-related research and treatment efforts.