Discovery reveals the guardian of the immune system: Ikaros

In a scientific breakthrough that helps us understand the internal wiring of immune cells, researchers at Monash University in Australia have cracked the code behind Ikaros, a protein essential for the development of immune cells and protection against pathogens and cancer.

This groundbreaking research, led by distinguished Professor Nicholas Huntington from Monash University’s Biomedicine Discovery Institute, is poised to reshape our understanding of genetic control networks and their impact on everything from eye color to susceptibility to cancer and the design of new therapies. The study, published in Natural immunologypromises crucial information on the mechanisms that protect us against infections and cancers.

When the transcription factor Ikaros/Ikzf1 was deliberately obstructed, whether in preclinical models or in humans, the once-potent activity of natural killer (NK) cells, the front-line warriors of our immune system, s is collapsed. Loss of this transcription factor in NK cells resulted in widespread dysregulation of NK cell development and function, preventing their ability to recognize and kill virus-infected cells and eliminate metastatic tumor cells from the circulation. .

Aiolos/Ikzf3 and Helios/Ikzf2, a related family member, were found to partially compensate for the loss of Ikaros. Thus, when multiple members of the IKZF family were inhibited, NK cells underwent rapid death. Mechanistically, Aiolos and Ikaros directly bind and activate most members of the JUN/FOS family, transcription factors known for their essential roles in human embryonic development and tissue function.

This discovery opens the door to the prospect of new potential treatments against cancer. NK cells, our first line of defense against pathogens and internal threats like cancers, could be boosted by therapies that enhance their killing prowess by targeting Ikaros and JUN/FOS biology.

Professor Huntington notes that drugs targeting Ikaros/Aiolos have already received approval from the US Food and Drug Administration (FDA) and the local Therapeutic Goods Administration (TGA) for the treatment of B-cell malignancies.

He noted: “But until now, we have not understood how these drugs work. Armed with this new information, it may be possible to develop new drugs targeting these complexes, which could offer pharmacology and a therapeutic index differentiated for the treatment of diseases.”

In this regard, Professor Huntington’s team was able to show that Ikaros plays a conserved role in healthy B cells and therefore potentially in B cell cancers.