When good cells go bad

Our primary defense against the outside world is our immune system. It is a complex system created with the sole purpose of protecting our bodies from various foreign invaders. Over many years of evolution, it has become particularly good at identifying, isolating, and eliminating potential threats. However, what if those same defenses turned on us? What happens when the immune system can no longer tell the difference between friend or foe? This occurs during autoimmune conditions, when the immune system attacks one’s own cells and tissues. To date, several disorders are linked to this condition; one example brought to light recently occurs during the onset of type 1 diabetes (T1D) in children. Evidence that regulatory CD4+ T cells (Tregs) suppress the activation of autoreactive T cells and maintain self tolerance has led to the hypothesis that Treg dysfunction is a major factor underlying the development of T1D (Sakaguchi et al.)

The best characterized Tregs are those that express the FOXP3 transcription factor, but although FOXP3 appears to be an accurate marker of Tregs in mice, it is also expressed by activated nonsuppressive T cells in humans (Ziegler et al.) This research, reported in the Journal of Immunology, demonstrated how dysfunctional Tregs are a key contributor to the onset of T1D in children. In humans, it has been shown that nonsuppressed T cells express a transcription factor FOXP3 and it has been established that cells that overexpress IL-17 can lead to T1D (Marwaha at el.) T1D patients have been shown to have elevated levels of IL-17-producing cells but there was no relevance shown. Recently other research groups have shown that cells that express FOXP3 can produce IL-17, and that Treg cells can transform into IL-17-producing cells (Voo et al.) This lead to a further discovery that a specific subset of Treg cells can avoid suppression and produce IL-17. This type of cell is known as (CD45RA^-, CD25^int, FOXP3^low). In this study, it is shown that populations of this particular subset is increased in patients with the onset of T1D. Overall, it is evident from this research that our greatest defense can also be our greatest threat if not regulated properly. Although this discovery could benefit T1D patients in the future, researchers have yet to come up with a strategy to circumvent this regulatory dysfunction.