In the operating room at the Children’s Hospital of Georgia, Drs. Jack Yu and Mohamad Masoumy put the final stitches into the face of a 5-month-old boy after repairing his cleft lip.
The plastic surgeons worked quickly but carefully with small deft movements as Yu told Masoumy that this “is an area where you don’t want to leave a big scar.” Another unlikely outcome from the common procedure is an infection at the site of the surgery, and Augusta University researchers can now explain why.
Yu and Dr. Barak Baban, an immunologist at the Dental College of Georgia, are part of a team that published a study that for the first time shows evidence of an innate class of immune cells in the tissues of the mouth and lips that protect the area and are likely the cause of historically low rates of infection from cleft lip and cleft palate surgeries.
The previously unsuspected cells, present in the gut and lungs and some other mucosal areas, also point to a potential for development as an alternative to the antibiotics quickly being overwhelmed and outflanked by resistant bacteria and could even provide other therapeutic potentials, such as treating obesity.
Researchers are just beginning to understand how they work and what systems they might be influencing, Baban said.
The cells, called innate lymphoid cells, are part of an ancient line of defense present from birth, but these cells were largely unrecognized until around nine years ago, Baban said. The problem is they lack the traditional markers on the cell surface that researchers use to search for immune cells, so they escaped the standard cell identification methods.
“They are different,” Baban said. “We said those cells are maybe debris or something.”
But once they were identified, they appear to have been there all along, Yu said.
“How to defend ourselves was present from way back,” he said. “This innate immunity is not something new. It has been around for a long time.”
They appeared to be associated with mucosal barrier area and were thought to be present mainly in the gut and lungs, Baban said. But using material left over from the cleft surgeries, the AU team went looking for them in the lip and mouth samples, Yu said.
“We looked for those immune cells. And by and large we did find them,” he said. “They behave like immune cells but they don’t have
the regular markers for B cells or T cells.”
The immune system has essentially two arms, an innate or natural system and the “acquired” system that learns to recognize threats and react, Baban said. These innate cells don’t need that “education” to spring into action, he added.
“It just by default reacts,” Baban said. “They are acting, reacting very fast.”
That they would be present in the oral area, even though no one had found them there before, just makes sense, Yu said.
“If you’re going to have border guards, you’re going to deploy them to the borders,” he said. “They were there from the beginning. Because the moment you pop out, you need to eat. The moment you eat, you get the bacteria.”
For Yu, the cells open up a lot of possibilities.
“From a clinical perspective, what I would like to know is can this kind of advantage be exported to other scenarios?” he said.
There is increasing antibiotic resistance that has narrowed effectiveness to around two years, Yu said. In the face of that, “rather than giving antibiotics, we will give you a dose of enriched innate lymphoid cells from your own body and let them do their thing,” Yu speculated. A similar strategy using altered T cells against resistant cancers is being tried in clinical trials, he said.
But there are still many unknowns about these cells, Yu said. For instance, other immune cells have elaborate strategies to avoid attacking healthy cells.
In the innate lymphoid cells, “armed with these kinds of tools, how come the natural killer cells don’t just go crazy and start killing regular cells?” Yu asked. “Where they specifically come from is not completely clear.”
There is intriguing evidence from mice that these cells go awry in diseases such as asthma in which an immune response has gone awry, Baban said. Manipulating them could help treat those kinds of diseases, he said. The cells are also greatly suppressed by obesity, so that could be another application where manipulating them could have an effect, Baban said.
“From the basic science perspective, they have a whole lot more questions to answer,” Yu said.