Nature sub-issue: Epithelial cells use MHC-II molecules to coordinate lung immunity

Lung immunity is essential to combat all lung diseases, including COVID-19, pneumonia, lung cancer, asthma, and chronic obstructive pulmonary disease
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Lung immunity is different from the focus of general biomedical research and intervention-systemic immunity, 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
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Researchers from Boston University School of Medicine (BUSM) found that the immune control in the lungs is accomplished by epithelial cells arranged in airspace, using a specialized immune-oriented molecule MHC-II

The barrier tissue is occupied by functional plastic CD4+ resident memory T (TRM) cells
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Whether the barrier epithelium regulates the location, plasticity and activity of CD4+ TRM cells is still unclear

"In the absence of epithelial MHC-II, repeated encounters with homologous antigens result in CD4+ TRM cells co-expressing several classic antagonistic lineage-defining transcription factors, changing their cytokine profile, and leading to barrier immune disorders
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In addition, lung epithelium MHC-II is necessary for the surface expression of PD-L1.

"Lung epithelial cells are usually expected to support respiratory function, and it is reported that mhc ii connects immune cells to immune cells.
Therefore, the discovery of lung epithelial cells mhc ii tells TRM cells where and what to do in the lungs is novel and unexpected," corresponding author Joseph Mizgerd explained that he is a professor of medicine, microbiology and biochemistry at BUSM
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Utilize human models and experimental models

By analyzing lung epithelial cells from humans and experimental models, the researchers learned that all different types of epithelial cells express MHC-II and increase its expression during infection
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The only known function of MHC-II is to educate immune cells called CD4+ T cells

Only interrupting MHC-II on lung epithelial cells results in abnormal number, type, and location of CD4+ T cells in the lung, rather than blood, indicating that these specific lung cells are responsible for directing lung immunity
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"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
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In addition to their protective effects in pneumonia, TRM cells are also fighting cancer.

In addition to showing that lung epithelial cells use the immune system in the lungs of MHC-II tissue, the study also revealed two unexpected findings derived from the main findings
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First, other immune-oriented molecules rely on MHC-II to reach the cell surface, where they can interact with other cells to complete immune commands

"This led to the discovery of these cancer treatments that the target of a molecule is a molecule that depends on mhc ii to obtain the cell surface, and it is suggested that inhibitor therapy from checkpoints may cause harmful side effects from the suppression of lung epithelial cells, immune cell-directed" Mizgerd Say

The researchers pointed out that interventions (including prevention and treatment) can be designed to use 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 and/or cancer, while at the same time be able to turn off their pathological effects during asthma when necessary," Shenoy explained
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