Researchers discover how smoke impairs lung immune cells

Prolonged exposure to cigarette smoke destroys the air sacs in mouse lungs (left). But this destruction is prevented in mice lacking MAIT cells (right).
Prolonged exposure to cigarette smoke destroys the air sacs in mouse lungs (left). But this destruction is prevented in mice lacking MAIT cells (right).
© 2025 Awad et al. Originally published in the Journal of Experimental Medicine. https://doi.org/10.1084/jem.20240896

While it has been known for decades that cigarette smoking is hazardous to lung health, researchers in Australia have discovered exactly how multiple chemicals found in cigarette smoke and e-cigarettes alter the function of a key type of immune cell found in the lungs.

In a study published in the Journal of Experimental Medicine, researchers found that these alterations can make cigarette smokers — and those exposed to secondhand smoke — more susceptible to respiratory infections. They can also worsen smoking-related inflammatory diseases like COPD.

The first author on the study, Wael Awad, PhD, of Monash University’s Biomedicine Discovery Institute, said in a news release that, “until now, the mechanisms underlying the skewed immune responses in people exposed to cigarette smoke and how they are related to smoke-associated diseases, like COPD, [have remained] unclear.”

The researchers looked at the effects of cigarette smoke on mucosal-associated invariant T (MAIT) cells, a type of immune cell in the lungs and other tissues of the body that helps fight off bacterial and viral infections and promotes inflammation or tissue repair.

These cells are activated by a protein called MR1, which recognizes chemicals produced by bacteria and presents them at the surface of infected cells to activate MAIT cells and initiate the immune response.

“We suspected that some of the more than 20,000 chemicals present in cigarette smoke that smokers inhale might also bind to MR1 and influence the activity of MAIT cells in the lungs,” Dr. Awad said.

Using computer modeling, the researchers were able to predict which components of cigarette smoke might be recognized by MR1. They found that several of these molecules not only bound to the protein, but also either increased or decreased the amount of the protein on the surface of the cells. The chemicals, which include benzaldehyde derivatives that are used as flavorings in cigarettes and e-cigarettes, blocked activation of human MAIT cells by compounds produced by bacteria.

The researchers then turned from computer models to studying the effects of the cigarette smoke on MAIT cells from both human blood and mice and showed that the smoke reduced MAIT cell function. Mice that were repeatedly exposed to cigarette smoke developed symptoms of lung disease, which was worsened if also infected by influenza. Researchers found that long-term exposure to cigarette smoke altered the protection provided to the mice by their MAIT cells, making them less able to fight off infections and more prone to the development of COPD.

The researchers now plan to investigate exactly which MAIT cell pathways are impacted by cigarette smoke to learn how to better treat COPD and other lung diseases.  

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