Zinc Deficiency Exacerbates Lead-Induced Interleukin-2 Suppression by Regulating CREM Expression

Lead, a prevalent heavy metal, impairs the immune system by affecting T cell function. Similarly, zinc deficiency adversely affects T cells, with zinc deficiency and lead exposure being linked to reduced interleukin-2 (IL-2) production. Zinc deficiency has been associated with increased expression of the transcription factor CREM 100 kDa, which downregulates IL-2. Previous research suggests zinc may mitigate lead's toxic effects. This study explored the molecular mechanism underlying IL-2 reduction in lead-exposed T cells and examined the role of zinc status. The effects of lead exposure were investigated in Jurkat T cells in zinc-adequate, zinc-deficient, and zinc-supplemented conditions. Results showed that lead exposure increased CREM 100 kDa expression, which was amplified under zinc-deficient conditions. Consequently, IL-2 production was significantly lower in cells exposed to both lead and zinc deficiency compared to lead exposure alone. However, zinc supplementation counteracted these effects, preventing CREM 100 kDa overexpression and restoring IL-2 levels. In conclusion, we identified CREM 100 kDa as a potential molecular mechanism behind the lead-induced IL-2 decrease in Jurkat T cells, with zinc deficiency exacerbating this effect. These findings highlight the protective role of zinc in counteracting lead toxicity and emphasize the importance of maintaining adequate zinc levels for immune health.