Nrf2 activation suppresses production of T cell cytokines and IgM in C57BL/6 mice (90.26)

• Published in: The Journal of immunology (1950) 2009-04, Vol.182 (1_Supplement), p.90-90.26
• Main Authors: Rockwell, Cheryl E, Fields, Patrick E, Crawford, Robert B, Kaminski, Norbert E, Klaassen, Curtis D
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.182.Supp.90.26

Nrf2 is a transcription factor that upregulates cytoprotective genes in response to cellular stress. Nrf2 gene expression is induced in CD3+ cells by tert-butylhydroquinone (tBHQ), a known Nrf2 activator. In addition, tBHQ upregulates the Nrf2 target genes, Ho-1, Nqo1, and Gclc in wild-type, but not Nrf2-null CD3+ T cells. Furthermore, tBHQ and butylated hydroxyanisole (BHA), another Nrf2 activator, markedly inhibit IFNγ transcription in wild-type activated T cells, but have little effect on IFNγ transcription in Nrf2-null T cells. Likewise, tBHQ inhibits binding to both the AP-1 and NFκB response elements in wild-type CD3+ cells, but only modestly inhibits AP-1/NFκB binding in Nrf2-null CD3+ cells. Production of TNFα and IL-2 by activated T cells is also suppressed by tBHQ. In accordance with the aforementioned findings, tBHQ-treated mice exhibited diminished antibody production to sheep RBC, a T cell-dependent immune response. Collectively, the current studies suggest Nrf2 activation in CD3+ cells markedly inhibits T cell cytokine production and consequently, T cell-dependent responses, in vivo. The present studies suggest Nrf2 may represent a novel regulatory mechanism in mature murine T cells and thus may be a useful target for the development of new anti-inflammatory therapeutics. (Supported by NIH grants ES09716, ES07079, ES013714, ES09649, and RR021940.)