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March 29, 2023

Learning How Tregs Keep Your Immune System in Check

The immune system keeps us healthy by maintaining a delicate balance. Every cell has a purpose: Some sound the alarm when they see an invader. Some attack germs that don’t belong. And some patrol the other cells in the immune system to make sure they’re doing their job.

Bad things happen when this balance is disrupted. When immune cells called T cells become overactive they cause autoimmune disease. When they are underactive it can lead to cancer. Scientists at BRI are honing in on the role Tregs (a rare, specialized type of T cell) play in maintaining this balance or letting it go awry.

“Tregs oversee how other T cells behave,” says BRI’s Steven Ziegler, PhD, who has studied Tregs for more than two decades. “They make sure T cells wait calmly until they are needed.”

Recently, his lab helped uncover the precise mechanism that Tregs use to maintain balance in the immune system.

Dr. Ziegler says, “This also sheds light on how the entire immune system is regulated — and it’s just really cool science.”

Exactly How Tregs Work

T cells go through a specific process when they sense an invader in the immune system. First, they build biomass and get ready to make all sorts of proteins. Then, they make a bunch of copies of themselves, which zoom to site of infection and stop it. They calm down again once the germs are gone.

Dr. Ziegler’s team built a model to examine exactly how Tregs affect this process. They started by turning off the Tregs.

“Without the Tregs, T cells just started ramping up and up and up and never stopped,” Dr. Ziegler says.

Then, they looked at how and when Tregs told T cells to calm down. That’s when they discovered that Tregs jump in right at the beginning, blocking the initial buildup of biomass and essentially shutting down the whole process before it even starts.

The researchers didn’t stop there. A team from the University of Washington, led by Ram Savan, PhD, detailed the role RNA plays in this process. Jing Song, PhD, from BRI’s Buckner Lab, showed that the same process found in the model also happens in humans. Now, she is analyzing this process in samples from people with autoimmune disease.

“Collaboration was crucial to this project. We each have very different areas of expertise, so analyzing the same mechanism from different angles helped us really understand this process,” Dr. Ziegler says. “Using Tregs to create a treatment for autoimmune disease is still a ways away, but everything we learn about them moves us a little closer.”

How TRegs Regulate T Cells

Inline - How TRegs Regulate T Cells
Scientists have long known that immune cells called Tregs help keep attacker cells called T cells in check. BRI’s team recently conducted research into exactly how they do that. When T cells prepare to attack, they start building biomass and ramp up to fight. The research team learned that Tregs jump in right at the beginning, when T cells start ramping up, and shut down the whole process.

Can TRegs Stop Immune System Disease?

Tregs could hold the key to more effective immune system disease treatments. In partnership with Seattle Children’s Research Institute, BRI researchers are using gene editing to turn T cells that cause autoimmune disease into Tregs that protect you from autoimmune disease. We’re also exploring the role Tregs play in cancer, starting with colon cancer research from Kazushige Ninomiya, PhD.

“We’ve actually seen Tregs protect cancer from the immune system, and if you disable Tregs it’s much easier to kill the tumor. It’s basically the opposite of autoimmune disease,” Dr. Ziegler says. “That’s the yin and yang of the immune system. So the more we know about the underlying mechanisms, the better insight we have into all of the diseases that impact the immune system.”

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