Zinc finger protein Helios is a protein that in humans is encoded by the IKZF2 gene. This protein is a member of Ikaros family of transcription factors.

This gene encodes a member of the Ikaros family of zinc-finger proteins. This family of transcription factors consists of five members: Ikaros (Ikzf1), Helios (Ikzf2), Aiolos (Ikzf3), Eos (Ikzf4), and Pegasus (Ikzf5). The Ikaros family members are involved in the hematopoietic development, some to a greater extent than others with Ikaros being expressed in all hematopoietic cells. This protein forms homo- or hetero-dimers with other Ikaros family members. Multiple transcript variants encoding different isoforms have been found for this gene, but the biological relevance of some variants has not been determined.

When these factors are missing or altered, lymphocytes suffer from defective development. Since Ikaros family members can interact with each other, it is probable that when one transcription factor is defected, others can substitute it. Because of this, it is rather difficult to assess precise function to each transcription factor.

Ikaros family members are characterised by having 4 N-terminal zinc finger domains, except for Pegasus, which has only 3. These are the key domains for DNA binding and stabilization of DNA-protein interactions. They also have C-terminal zinc finger domains which serve as a site for interactions with other proteins and hetero- or homodimerization with other family members.

Helios is said to repress the IL-2 expression in Tregs. This function was also confirmed for Eos, another member of Ikaros family of transcription factors, pointing to their redundant functions. Helios interacts with Foxp3 to lower IL2 expression. They form a complex and bind to the IL2 locus causing repressive epigenetic modifications, namely reduced histone H3 acetylation. Loss of Helios causes decreased binding of Foxp3 to the IL2 promoter and milder IL-2 repression.

Helios is also said to be part of the positive feedback loop of IL-2. It positively affects the IL-2Rα-STAT5 pathway. IL-2 maintains Helios expression. IL-2 is probably not the only factor positively affecting Helios expression.

Helios is said to also function as a tumor suppressor. Such role of Helios was observed when a dominant negative isoform of this protein, that lacked three out of four N-terminal zinc fingers, was found in adult T cell malignancies. Indeed, forced expression of this isoform of Helios did lead to the development of T cell lymphoma in a murine model. However, the ectopic expression of wildtype Helios in B cells results in lymphomas as well. This suggests that Helios might act as a tumor suppressor only in the cells that it is naturally expressed in, when expressed in other cells, it is rather tumorigenic.

Since Helios-deficient Tregs have the ability to produce IFN-γ and TNF-α, they seem to be useful in anti-tumor responses. Such Treg cells can infiltrate the tumor without keeping their suppressive function, subsequently producing IFN-γ and TNF-α, which could help with slowing the tumor growth. Moreover, the loss of suppressive phenotype of Treg cells was observed in tumors, but not in splenic Tregs, which can potentially have great clinical significance. Based on these findings, Helios could be considered a powerful tool in the anti-tumor therapy. However, it is too early for such conclusion and even though the data seem promising, more research needs to be done in this area.