JDRF Research

Protein Switches Partners to Change immune Function Immune

A single protein can switch a key component of the immune system on or off depending on which molecule it teams with, JDRF-funded researchers have found. The protein, NFAT, pairs with other proteins to either spur immune cells into attack mode or
direct them to stand down.

The discovery helps us understand what is involved in keeping the immune system in check, paving the way for researchers to develop therapies for type 1 diabetes and other autoimmune afflictions such as arthritis and allergies. The finding also could be an important step toward learning how to manipulate the expression of individual genes.

NFAT is a “transcription factor,” one of about 3,000 proteins that help translate a gene’s code into active proteins that carry out various cellular functions. JDRF researchers found that NFAT collaborates with another transcription factor, FOXP3, to orchestrate gene expression necessary for immune tolerance, preventing an attack on the body’s own cells. However, when NFAT pairs with a third transcription factor, AP-1, it stimulates
an immune attack. Depending on its partner, NFAT turns the immune response on or off.

The finding was reported by Anjana Rao, Ph.D., and colleagues at the JDRF Center for Immunological Tolerance in Type 1 Diabetes at Harvard Medical School. Researchers at the University of Southern California, the University of Colorado, and the University of Washington were also involved in the investigation, which was published in the journal Cell (Vol. 126, p. 375, 2006).

In the study, the researchers showed in mice that disrupting the interface between NFAT and FOXP3 resulted in a loss of immune tolerance. As a result, these mice developed the disease much more quickly than mice whose NFAT-FOXP3 interface was left undisturbed.

“These findings provide insight into the delicate balance between immune activation and suppression,” said JDRF Director of Immunology Teodora Staeva-Vieira, Ph.D. “Importantly, they also identify the nexus between NFAT, AP1 and FOXP3 as a novel therapeutic target for immune intervention.”