Research Alert

A Yale School of Medicine study sheds new light on the complex signaling system immune cells use to coordinate responses to infection and cancer.

A team in the lab of David van Dijk, PhD, developed a software tool, CINEMA-OT (Causal independent effect module attribution + optimal transport), which allows researchers to examine an individual cell's response to different combinations of cytokines. Cytokines are small proteins, released by cells, which regulate inflammation.

“Tracking cellular responses is challenging as the process of measuring cells is destructive," says Dr. van Dijk, also a senior author of the study. "To solve this problem, we built a new algorithm using ideas from causal inference to match cells between experimental conditions and infer how cells respond to signals."

CINEMA-OT revealed that some cytokines have a different, synergistic effect on a cell's gene expression when used in combination with one another. Different combinations of cytokines represent a kind of code or language cells use to coordinate an immune response. “Deciphering the rules of cytokine signaling will allow better understanding and manipulation of immune responses for emerging immunotherapies,” says senior author Jeffrey Ishizuka, MD, DPhil.

The team also used CINEMA-OT to examine the impact of cigarette smoke on the immune response. Researchers found suppressed antiviral defenses in lung tissue after it was exposed to cigarette smoke.

CINEMA-OT is an open-source tool and is available for use at the van Dijk lab's website.

Journal Link: Nature Methods, Nov-2023