(EA02-01-25) The Plant-derived Compound Sulforaphane Decreases Expression of Activation Markers and IL-2 in Activated Jurkat T Cells

Scientific conference where the work was recently presented: FSHN Spring Awards Ceremony (Michigan State University)

Date on which the work was previously presented at the scientific conference listed: April 9, 2025

Objectives: Sulforaphane (SFN), a bioactive compound found in cruciferous vegetables, has gained considerable interest for its ability to activate the transcription factor Nrf2.  Numerous studies indicate that Nrf2 activation can modulate immune responses, including effects on T cell activation. Previous work in our lab demonstrated that tert-butylhydroquinone (tBHQ), a common food preservative and Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) activator, suppresses early T cell activation events, including interleukin-2 (IL-2) production, CD25 expression, and calcium influx. Building on these findings, this study explores the effects of sulforaphane, a naturally occurring isothiocyanate and potent NRF2 activator, on Jurkat T cell activation and function.

Methods: Using Jurkat T cells as a model, we compared the impact of tBHQ and SFN on key T cell activation events. Wildtype and NRF2-null Jurkat T cells were treated with 1, 3, 5, 10, 15, and 20 µM of either L-SFN or DL-SFN, as well as 0.1, 1, 5, and 10 µM of tBHQ, following activation with anti-human CD3 and CD28 for 24 hours. T cell activation was assessed by measuring cell surface markers (CD25, CD69, OX-40, CD40L, CD80, and CD86) using flow cytometry and IL-2 cytokine secretion via ELISA. 

Results: The data indicate that both L-SFN and DL-SFN decrease upregulation of the T cell activation markers, including CD25, CD69, CD134, CD154 and CD86, by activated Jurkat T cells. In general, these effects were comparable to the effects of tBHQ. While most of the effects of L-SFN and DL-SFN were observed in both wild-type and Nrf2-null Jurkat T cells, the decrease in CD134 expression by L-SFN and DL-SFN is Nrf2-dependent. L-SFN and DL-SFN also caused a significant suppression of IL-2 secretion by activated Jurkat T cells, which was consistent with the effects on activation markers.

Conclusions: Overall, this study shows that both L-SFN and DL-SFN suppress upregulation of activation markers and secretion of IL-2 by activated Jurkat T cells with most effects occurring in the 10 – 20µM range. The data also show that most of the effects occur independently of Nrf2.

Funding Sources: National Institutes of Health (1R01ES035763 to C.E.R.)