Tregs
Treg cells are a population of T cells that can suppress the effector function of other immune cells.[13] 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+.[8]
Helios is expressed only in 70-80 % of Treg cells in mice and humans. The fact that Helios is not expressed in all Tregs was in the past explained by the observations that Helios could actually be found only in tTregs (Tregs that arise from the thymus), not pTregs. This believe was supported by experimental data, that discovered the expression of Helios only in early Foxp3+ thymocytes or that did not find the expression of Helios in Tregs in the periphery in the first few days. Moreover, experiments generating induced Tregs (iTregs) in vitro, did not find any expression of Helios in the cells. Thus, Helios used to be considered a tTreg marker.[8]
Recently, the idea of Helios as a tTregs specific marker, has become controversial. Current studies indicate that even iTregs can express Helios transcription factor. Thus, it is unclear whether Helios can be used as a marker for tTregs.[8][13]
Current data suggest that Helios is a marker of Treg stability rather than a specific marker for differentiation between tTregs and pTregs.[11]
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.[11]
Tregs that lack Helios have lower expression of Foxp3 and lower activation of STAT5. Helios-deficient Tregs also seem to produce effector cytokines that are not usually produced by this cell type – interleukin 17 (IL-17), interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α).[10] 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.[11]
