Nature: How do Lung epithelial cells control lung immunity?
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Nature: How do Lung epithelial cells control lung immunity? This will lay the foundation for the treatment of many lung diseases!
Lung immunity is essential to combat all lung diseases, including COVID-19, pneumonia, lung cancer, asthma, and chronic obstructive pulmonary disease (COPD).
Lung immunity is different from systemic immunity. Systemic immunity is the focus of biomedical research and intervention, but most of the factors that affect the establishment and regulation of lung immunity are still unclear. Now, a new study reveals the role of lung cells in guiding the immune system.
The research paper was published yesterday (October 5) in the journal Nature Communications, and the paper is titled “Antigen presentation by lung epithelial cells directs CD4 TRM cell function and regulates barrier immunity+”
Researchers at Boston University School of Medicine (BUSM) discovered that the immune control of the lungs is accomplished by epithelial cells using a special immune-oriented molecule, MHC-II. This epithelial MHC-II is essential for locating and programming a highly specialized immune cell called Tissue Memory T (TRM) cells in the lung.
“In people’s usual expectation, the function of lung epithelial cells is to support breathing, while MHC-II connects immune cells with immune cells. Therefore, MHC-II on lung epithelial cells instructs TRM cells where to go and what to do. This discovery is novel and unexpected.” Corresponding author Dr. Joseph Mizgerd explained, he is a professor of medicine, microbiology and biochemistry at BUSM.
By analyzing lung epithelial cells in humans and experimental models, the researchers learned that all different types of epithelial cells express MHC-II and increase its expression during infection. The only known function of MHC-II is to cultivate immune cells called CD4+ T cells. In cell culture, lung epithelial cells can use this molecule to tell T cells what to do so that they can respond appropriately to microorganisms that may cause infection. Disrupting MHC-II only on lung epithelial cells will result in abnormal numbers, types, and locations of CD4+ T cells in the lungs, rather than in the blood, indicating that these specific lung cells are responsible for guiding lung immunity.
“Our research shows that lung epithelial cells are similar to gatekeepers. Their task is to appropriately indicate the location of CD4 TRM cell sentinels and their ability to fight future infections. Considering that TRM cells are not only protective in pneumonia, they are also fighting Cancer and asthma play a key role, and our findings are of great significance in understanding, preventing and treating a variety of lung diseases.” said Dr. Anukul Shenoy, a postdoctoral scientist at the BUSM Lung Disease Center and the first author of the research paper.
In addition to showing that lung epithelial cells use MHC-II to organize the lung’s immune system, the study also revealed two unexpected findings that stem from the main findings.
First, other immune-oriented molecules rely on MHC-II to reach the cell surface, where they can interact with other cells to execute immune commands. Second, the lack of MHC-II in lung epithelial cells can lead to changes in the local lung immune system, which reflects the rare but serious results of immune-targeted cancer therapy (“checkpoint inhibitor therapy”). “This has led to the discovery that the molecular target of these cancer treatments is one of the molecules that rely on MHC-II to reach the cell surface, and that the harmful side effects of checkpoint inhibitor therapy may be the result of lung epithelial cells instructing and suppressing immune cells.” Mizgerd Say.
The researchers imagine that interventions (preventive and therapeutic measures) can be designed to take advantage of the ability of lung epithelial cells to regulate lung immunity. “In this way, we will be able to use the patient’s own lung epithelial cells to turn on the protective effects of TRM cells during pneumonia or cancer, and at the same time to turn off their pathological effects during asthma when necessary,” Shenoy said.
Reference materials:
https://www.nature.com/articles/s41467-021-26045-w
Nature: How do Lung epithelial cells control lung immunity?
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