New research reveals role of lung cells in lung immunity

Pulmonary immunity is essential for fighting all lung diseases, including COVID-19, pneumonia, lung cancer, asthma, and COPD. Although pulmonary immunity differs from systemic immunity, which is the usual focus of biomedical research and intervention, little is known about the factors that influence the establishment and regulation of pulmonary immunity. New research is now revealing the role of lung cells in inducing the immune system.

Researchers at the Boston University School of Medicine (BUSM) have found that immune control in the lungs is obtained by cells that line the airspace. Epithelial cellsUses MHC-II, a molecule that faces particular immunity. This epithelial MHC-II is essential for highly specialized localization and storyboarding Immune cells They are called resident memory T cells (TRMs) in the lungs.

“Epithelial cells lung While MHC-II is believed to connect immune cells to immune cells, the discovery that MHC-II tells TRM cells where and what to do in lung epithelial cells is new and unexpected. is. “Corresponding author Joseph Mizgerd, ScD, professor of medicine, microbiology and biochemistry at BUSM, explained.

By analyzing lung epithelial cells from human and experimental models, the researchers learned that all of the different types of epithelial cells examined express MHC-II and increase its expression during infection. The only known function of MHC-II is to educate immune cells called CD4 + T cells. Cell cultureLung epithelial cells can use this molecule to tell T cells what to do, so they can respond appropriately to microorganisms that can cause infection. Blocking only MHC-II in lung epithelial cells results in abnormal numbers, types and locations of CD4 + T cells in the lungs, and these specific lung cells, and not blood, are involved in inducing l pulmonary immunity. It became clear.

“Our study shows that lung epithelial cells look like gatekeepers responsible for properly directing the location of CD4 TRM cell outposts and their ability to fight future infections. TRM cells Beyond its protective role in pneumonia, it plays an important role in the fight against cancer. It causes asthma and our results have a major impact on the understanding, prevention and treatment of multiple lung diseases. Said Dr Anukul Shenoy, senior author and doctoral researcher at BUSM’s Lung Center.

In addition to showing that lung epithelial cells are organized using MHC-II Immune system In the lungs, this study also reveals two unexpected findings resulting from the main findings. First, other immune molecules depend on MHC-II. Cell surface They can interact with other cells to provide immune guidance. Second, the absence of MHC-II in lung epithelial cells impairs the local immune system, reflecting the rare but serious consequences of immune-targeted cancer treatment (“checkpoint inhibitor therapy”). to augment. “This revealed that the molecular targets of these cancer treatments are one of the molecules that depend on MHC-II to reach the cell surface, and the harmful side effects of checkpoint inhibitor therapy on immune cells.” . It has been suggested that this could be due to inhibition. Guidance by pulmonary epithelial cells. “

Researchers believe that interventions (both preventive and therapeutic) can be designed to harness the ability of lung epithelial cells to regulate pulmonary immunity. “Then the patient’s own lung epithelial cells can be used to activate the protective role of MRT. cell During pneumonia and / or cancer, during asthma, and while being able to block their pathological role as needed, ”said Shenoy.

These results will be posted online in the journal Nature Communication..

For more information:
Antigen presentation by pulmonary epithelial cells directs the function of CD4 + TRM cells and regulates barrier immunity. Nature Communication (2021).