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May 7, 2025

A New Approach to Autoimmune Disease Treatment Takes a Big Step Forward

Primary biliary cholangitis (PBC) is a rare and little-understood autoimmune disease that affects the liver. It most commonly affects middle-aged women and there are few effective treatments. For some people, it leads to end-stage liver failure and the need for a liver transplant.

Ritika Tewari
Ritika Tewari, PhD

“Even then, immune cells may attack the new liver and the disease can come back,” says Ritika Tewari, PhD. “That’s why finding better treatment strategies is so important.”

Dr. Tewari and BRI’s Soo Jung Yang, PhD, recently published findings that could pave the way to better autoimmune disease treatment options. Their work focuses on a new approach that BRI’s Buckner Lab is pio­neering: turning T cells that contribute to autoimmune diseases into regulatory T cells (Tregs, pronounced “tee-regs”) that help prevent autoimmune diseases.

“This is an exciting advance because our goal is to apply this approach to many different autoimmune diseases — whether common or rare — in hopes of offering a more targeted and effective treatment,” Dr. Tewari says.

Graphic Layout Tregs in Health and Disease

Using Your Own Cells To Fight Autoimmune Disease

This work builds on decades of research that started when scientists began to understand the crucial role Tregs play in controlling (aka regulating) T cells, which are the immune cells that attack germs. When Tregs aren’t working properly, T cells can go into overdrive and attack healthy tissue and cause autoimmune disease.

This grasp of Tregs got BRI President Jane Buckner, MD, and other scientists thinking: Could we reprogram T cells — turning them into Tregs — to curb autoimmune diseases?

A similar approach is already being used in immunotherapies to treat cancer. Reprogramming a person’s own cells to fight cancer is more precise — and potentially less harmful than traditional treatments like radiation and chemotherapy.

Soo Jung Yang
Soo Jung Yang, PhD

“Because Tregs are so specialized, this approach would offer a highly targeted treatment for autoimmune diseases,” Dr. Buckner says. “For example, if T cells are attacking the joints, we can reprogram those cells to protect the joints from rheumatoid arthritis. This new treatment approach would only affect disease-causing cells, not the whole immune system.”

In 2022, a team led by Dr. Yang advanced this work when they demonstrated that this approach could prevent type 1 diabetes in lab models.

Dr. Yang and Dr. Tewari then asked the next question: Could this approach also treat or prevent other autoimmune diseases? They mapped out a study to see if this approach might work to treat PBC.

Engineering Tregs

Dr. Tewari teamed up with research technician Ethan McClain, leading the first phase of the study, teaming up to identify the specific peptide — a tiny fragment of a protein — that the T cells attack in PBC. 

Then, Dr. Yang led the next step: Edit that T cell’s genes so it becomes a Treg and stops attacking. The hope was that adjusting the approach that Dr. Yang had developed for T1D would also work for PBC — and it did. Their work demonstrated that engineered Tregs can help control PBC and prevent liver damage in lab models.

“It was really exciting to see all of the data come together,” McClain says. “It’s like following a recipe step by step, and at the end you get to see the final product.”

This is a big step toward the research team’s ultimate goal.

“Every disease has nuances. But this study demonstrates that if we can identify the disease-causing targets within the cells, we can likely apply this approach to other autoimmune diseases,” Dr. Tewari says. “That’s our ultimate goal. Every study gets us a little bit closer.”

Graphic Layout Engineered TRegs Lupus

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