The immune system is tightly regulated to ensure that it only responds to actual health threats, instead of attacking our own bodies, which happens in cases of autoimmunity. Now, researchers from Japan report a new protein–protein interaction that could account for some autoimmune conditions and suggest new avenues for treatment. In a study published this month in Immunity , researchers from Osaka University have revealed that interaction between two transcription factors is required for certain immune cells to behave appropriately.
Regulatory T cells (Tregs) help keep the immune system from kicking in at inappropriate times and causing autoimmune disorders or other negative effects. Treg function is mainly controlled by a protein called Foxp3 that activates the expression of some genes and represses the expression of others. "Previous studies have shown that the transcription factor Ikaros (encoded by Ikzf1) interacts with Foxp3, and that mutations in IKZF1 also cause immunodeficiency and autoimmune diseases, similar to those seen with Treg dysfunction," says lead author of the study Kenji Ichiyama.
"However, it was unclear how Foxp3 and Ikaros interact to affect gene transcription and alter the behavior of Tregs." To address this, the researchers first identified the region of Ikaros that is required for binding to Foxp3. They then deleted this region and expressed the deletion mutant in the Tregs of live mice.
"The results were striking," explains Shimon Sakaguchi, senio.