Arsenite induces dysfunction of regulatory T cells through acetylation control of the Foxp3 promoter

Abstract

Arsenic is known to cause damage to the body’s immune system by inducing epigenetic changes. However, the molecular mechanism of this damage remains elusive. Here, we report that arsenic disrupts the morphology of lymphocytes, decreases cell viability, and results in abnormal proportions of T lymphocyte subsets. Moreover, our results revealed that arsenic can reduce global acetylation of histone H4 at K16 (H4K16 ac) in lymphocytes via decreasing the level of males absent on the first but upregulates mRNA and protein levels of the forkhead/winged-helix box P3 ( Foxp3) gene by increasing the acetylation of histone H4 at K16 (H4K16) at the promoter of Foxp3. Finally, arsenic-induced dysfunction of regulatory T cells (Tregs) could be ameliorated by trichostatin A. Our research indicates that arsenic-induced immunosuppressive effect in human lymphocytes may be related to the acetylation of H4K16 at the promoter of Foxp3 and that histone deacetylase inhibitors may play a role in the prevention and treatment of immune injury caused by arsenic.

LncRNA MALAT1/calpain-1 axis in ATO/hypoxia induced hERG channel deficiency

“…As for the upstream of MALAT, or the molecular basis of enhanced expression of MALAT1, we found that it can be attributed to the increased acetylation level of the transcription factor foxo1 under the administration of ATO or hypoxia. It has been previously reported that arsenic can remarkably promote histone acetylation [23][24][25] through inhibiting the enzyme activity of the deacetylase HDAC [23] or RNA epigenetics [25], and so on. Therefore, ATO may enhance the acetylation level of foxo1 through the above pathways.…”

Detoxification of Selenium Yeast on Mycotoxins and Heavy Metals: a Review

“…Similarly, lead treatment also significantly inhibited the activities of SOD, GPX, and CAT and increased the accumulation of nitric oxide (NO) and MDA to induce oxidative stress and activate MAPK/NF-ĸB signal pathway to cause splenic necrosis [ 102 ]. Arsenic can disrupt lymphocyte morphology, reduce cell viability, cause abnormal proportions of T lymphocyte subsets, and induce regulatory T cell (Tregs) dysfunction to cause immune damage [ 103 ]. Liu et al found that chickens exposed to arsenic showed a reduced IFN-γ/IL-4 ratio and an increased IL-17 level, which indicated an imbalanced immune response in vivo [ 104 ].…”