University of Florida Health researchers find new details of immune system’s molecular “switch”

Dorina Avram, Ph.D., is a preeminence professor and associate chair of the UF College of Medicine’s department of anatomy and cell biology. Each day, a battle rages inside the body. Our immune system fights off infections but, in patients with certain medical conditions, it can also become overactive and damage vital organs. Now, a group led by a University of Florida Health researcher has found out how one molecular “switch” influences the immune system — a finding they say has major implications for future treatments for immune system diseases and cancer.

The research focused on a subset of cells that prevent the immune system from overreacting by producing antibodies that attack normal body tissues. The absence of a specific gene — known as Bcl11b — in regulatory T (Treg) cells triggers fatal systemic inflammation in mice, the researchers found. The results are published today in the journal Science Advances.

Autoimmune diseases are disorders that cause the immune system to attack normal body tissues.

Knowing how the Treg cells function is essential to long-term therapies that could be developed for autoimmune diseases, said Dorina Avram, Ph.D., the study’s lead author, a professor in the UF College of Medicine’s department of anatomy and cell biology and a member of the UF Health Cancer Center.

When the Bcl11b gene is absent, Treg cells are unable to function normally to control multi-organ inflammation in the lungs, liver, skin and kidneys, the researchers found. While the gene is crucial to the immune system’s normal function, having less of it can sometimes be beneficial. When cancer tumors arise, Treg cells can blunt the body’s natural immune response to the rogue cells. Manipulating the Bcl11b gene could be a way to unleash the immune system to properly target tumor cells, the researchers noted.

To establish their findings, the researchers studied two groups of mouse models. Compared with a control group, those that lacked the Bcl11b gene showed symptoms of fatal autoimmunity and died at an early age. Those findings showed that the gene is essential for supporting normal regulatory T-cell function.

Using human Treg cells, the researchers also demonstrated that a particular and crucial genetic mechanism works the same way in mice and humans. That discovery, Avram said, is important for translating future research findings into therapies for people.

Next, researchers want to learn more about how Bcl11b controls Treg cells and identify the regions of genetic material, known as enhancers and silencers, that it controls, Avram said. After that, research could focus on how such genomic regions are linked to particular autoimmune diseases including those in humans, she said.  

The study’s first co-authors are Theodore T. Drashansky and Eric Helm, who are doctoral students in the UF College of Medicine’s department of anatomy and cell biology. Other collaborators include researchers from the UF College of Public Health and Health Professions’ department of biostatistics, the UF College of Veterinary Medicine and Albany (N.Y.) Medical College. The study was supported by funding from the UF Health Cancer Center and the National Institutes of Health (NIH grants R01AI067846, R01AI078273, R21AI13120501, R01DK105562, 2T32DK074367 and T32AI007110).    

About the Author

Doug Bennett's picture

Doug Bennett

Science Writer, Editor

Doug Bennett joined the UF Health staff in January 2015 as a science writer and editor. His topic areas include anatomy; biochemistry and molecular biology; molecular genetics and microbiology; pathology,...Read More