Researchers at The Scripps Research Institute in La Jolla, California, discovered a new type of immune cell that’s predisposed to become a regulatory T regulatory, or Treg cells, countering immune reactions. The finding has far-reaching implications for autoimmune diseases such as type 1 diabetes, where it could potentially generate new treatment development.
The body’s immune system is composed of many types of cells, still rather poorly understood by scientists. While researchers know about certain types of immune cells and some of their functions, the immune system’s strategy of combining cell surface molecules and generating receptors through genetic rearrangements make immune cells a difficult study subject.
T-cells are one of those cells that, albeit casually grouped together, can have strikingly different properties. Treg, one type of T-cell, is crucial for controlling and resolving immune responses.
In their work studying Tregs, the Scripps team, led by biologist Oktay Kirak, isolated a single Treg from a mouse model of type 1 diabetes. They removed its nucleus, containing the genetic information unique to this kind of Treg, and inserted it into a mouse egg cell after removing its own nucleus.
Published in the journal Proceedings of the National Academy of Sciences (PNAS), their study, “Nuclear transfer nTreg model reveals fate-determining TCR-β and novel peripheral nTreg precursors,“ showed how the team, in this way, engineered a mouse model capable of producing only this kind of T-cell. This allowed them to study in detail how the cells are generated, as well as their function.
The cell turned out to be a so-called natural-arising Treg (nTreg), originating in the primary immune cell-producing organ — the thymus. Even though the mouse was only supposed to produce one T-cell type, the researchers noted that a second type emerged in the thymus and spleen of the animal.
“We realized that the one T-cell type exists in two functional states,” Kirak said in a press release. “That was a huge surprise — I didn’t believe it at first.”
While repeating the experiments several times to make sure the finding was real, the team discovered that although the cells were genetically identical, one of them had switched on a gene called FoxP3. This, it turned out, was the difference needed for a pre-nTreg – looking like any conventional T-cell – to turn into an nTreg.
“This study was eye-opening,” Kirak said. “You wouldn’t expect these cells to have this ability. The best analogy I have is Clark Kent turning into Superman. Clark Kent looks like an Average Joe, so no one would expect him to have the same abilities as Superman.”
The scientists believe these pre-nTreg cells might be activated under certain circumstances, such as when the immune system is challenged by infections, cancer, or in autoimmune diseases.
If researchers could find a way to make the body produce more nTregs, the knowledge might be used as a new way to treat autoimmune diseases such as type 1 diabetes, where Tregs fail to launch a sufficient response to immune cells incorrectly attacking insulin-producing cells.
Kirak’s lab will now focus on developing markers to distinguish various Treg and pre-Treg types. They also plan to use the technique for studying cancer-related immune cells.