Jorg Goronzy

Publication Details

  • Decline in miR-181a expression with age impairs T cell receptor sensitivity by increasing DUSP6 activity NATURE MEDICINE Li, G., Yu, M., Lee, W., Tsang, M., Krishnan, E., Weyand, C. M., Goronzy, J. J. 2012; 18 (10): 1518-U113

    Abstract:

    The ability of the human immune system to respond to vaccination declines with age. We identified an age-associated defect in T cell receptor (TCR)-induced extracellular signal-regulated kinase (ERK) phosphorylation in naive CD4(+) T cells, whereas other signals, such as ? chain-associated protein kinase 70 (ZAP70) and phospholipase C-?1 phosphorylation, were not impaired. The defective ERK signaling was caused by the dual specific phosphatase 6 (DUSP6), whose protein expression increased with age due to a decline in repression by miR-181a. Reconstitution of miR-181a lowered DUSP6 expression in naive CD4(+) T cells in elderly individuals. DUSP6 repression using miR-181a or specific siRNA and DUSP6 inhibition by the allosteric inhibitor (E)-2-benzylidene-3-(cyclohexylamino)-2,3-dihydro-1H-inden-1-one improved CD4(+) T cell responses, as seen by increased expression of activation markers, improved proliferation and supported preferential T helper type 1 cell differentiation. DUSP6 is a potential intervention target for restoring T cell responses in the elderly, which may augment the effectiveness of vaccination.

    View details for DOI 10.1038/nm.2963

    View details for Web of Science ID 000309587500030

    View details for PubMedID 23023500

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