Organisms are protected against diseases by their immune system. As a complex network of organs, cells, and proteins, the immune system detects and responds to various pathogens, distinguishing them from the organism's healthy cells. In a recent study, scientists discovered that the immune system also receives protection against invaders from a special type of protein.
Researchers at Monash University have made a scientific discovery breakthrough that improves our understanding of the internal wiring of immune cells. Led by eminent Professor Nicholas Huntington of the Biomedicine Discovery Institute, the research team focuses on Ikaros, a protein that plays an important role in developing and protecting cells against pathogens and cancer. The result of the study is discussed in the paper "IKAROS and AIOLOS directly regulate AP-1 transcriptional complexes and are essential for NK cell development."
Understanding Immune Responses
Studying the nature of Ikaros provides important insights into the mechanisms that protect us against infections. It helps reshape our understanding of gene control networks and their impact in designing novel therapies.
It has been known that Ikaros transcription factors are vital for adaptive lymphocyte function, yet their role in innate lymphopoiesis remains a mystery. By using conditional genetic inactivation, the researchers demonstrated the importance of ikzf1/Ikaros for normal natural killer (NK) cell lymphopoiesis.
When the researchers deliberately obstructed these transcription factors, be it in preclinical models or humans, the activity of natural killer cells dropped significantly. The loss of Ikaros transcription factors in natural killer cells resulted in widespread NK cell development and function dysregulation. This prevents their ability to recognize and defeat virus-infected cells and clear metastatic tumor cells from circulating.
Related family members, Aiolos/lkzf3 and Helios/lkzf2, were also partially found to compensate for the Ikaros loss. When multiple members of the lkzf family are inhibited, the natural killer cells die rapidly. Aiolos and Ikaros were also found to bind and activate most JUN/FOS family directly members, the transcription factors known for their crucial roles in embryonic development and tissue function in humans. This discovery paves the way for the development of new therapies against cancer.
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Ikaros as Transcription Factor
Ikaros refers to a DNA-binding protein encoded by the IKZF genes of the Ikaros family zinc finger group. The zinc finger enables protein binding to DNA or RNA molecules as a minor structural motif.
The IKZF family comprises five members: Ikaros, Helios, Aiolos, Eos, and Pegasus. Ikaros is derived from a boy's name from ancient Greek lore. It is a variation of "Icarus" and implies a pioneering spirit.
Ikaros displays crucial functions in the hematopoietic system and is known for being a regulator of the development of early B cells. It was also found to be a major tumor suppressor involved in human B-cell acute lymphoblastic leukemia. Additionally, it is important in the differentiation and function of individual T helper cells.
Dysfunction of Ikaros is linked to the development of chronic lymphocytic leukemia. It affects the expression of B cells, which can lead to the deregulation of the BCR signaling during B cell development, resulting in increased cell apoptosis.
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