Scientists at UCLA have decoded the “vocabulary” of immune cells—six distinct signals used as flares to deploy immune defenses.
In the study, published in the peer-reviewed journal Immunity, researchers found that the use of the wrong signals can lead to the activation of the wrong genes, initiating autoimmune diseases.
“Cells have evolved an immune response code, or language,” said senior author Alexander Hoffmann.
“We have identified some words in that language, and we know these words are important because of what happens when they are misused. Now we need to understand the meaning of the words, and we are making rapid progress. It’s as exciting as when archaeologists discovered the Rosetta stone and could begin to read Egyptian hieroglyphs.”
The immune system coordinates its security efforts by using unique signaling codons, the “words” that communicate which genes to express to best eliminate a specific threat. Upon closer inspection, the research team decoded the signaling codons used by immune cells that correlated to specific pathogens. They also analyzed the same signals in a mouse model of an autoimmune condition called Sjögren’s syndrome.
“Indeed, we found defects in the use of two of these words,” Hoffmann said. “It’s as if instead of saying, ‘Respond to attacker down the street,’ the cells are incorrectly saying, ‘Respond to attacker in the house.’”
These findings were a result of an exhaustive search, which saw the scientists analyze over 12,000 cells, tracking their signals in response to a panel of 27 immune threats. The team relied on a machine learning algorithm to model the immune responses of the macrophages, which led them to the discovery that all six words were critical for mounting the appropriate immune response.