As transcription factor 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.
IL-2 maintains Helios expression.
IL-2 is probably not the only factor positively affecting Helios expression. We can divide
Treg cells into two main subsets: thymus-derived Treg cell (tTreg) and peripherally-induced Treg cell (pTreg). TTregs are the subset of cells that develops in
thymus from
T lymphocytes that recognise self-antigens. Whereas pTregs are
lymphocytes that are induced in the periphery originally from
CD4+ Foxp3- cells and which subsequently acquire suppressive function. Both
Treg cells subsets are
Foxp3+. It was discovered that Helios is not essential for early development of
T cells in
thymus, but it is important for
Treg suppressive function later in their life. This conclusion was drawn when the loss of Helios in
T cells did not have any effect on
T cell development and
homeostasis of the
immune system in a mouse model. However, it did result in a defective immune regulation later in the life with the onset of
autoimmunity resulting from defective
Treg function. Thus, this suggests that Helios is important for the identity of
Treg cell and stability of their
cytokine profile. It is important to mention, that so far we do not have enough knowledge about the mechanism of Helios keeping
Treg stability and even about Helios's own expression in
Tregs. Thus, there is a need to uncover the mechanism behind these findings.
In other immune cells Beside
CD4+ Tregs, Helios is also expressed in murine
NK cells. In this immune cell subset, Helios is expressed early during their development, and it is later downregulated. Helios is also expressed in
CD8+ regulatory T cells. Helios maintains their suppressive function similarly to the
CD4+ Tregs. == References ==