Abstract: Substantial evidence supports that T-cells play a central role in the pathogenesis of systemic lupus erythematosus (SLE). To explore the molecular basis of the defective function of SLE T-cells, we focused on the signal transduction system via T-cell antigen receptor (TCR) in peripheral blood T-cells from SLE patients. Comprehensive analysis to identify the molecules responsible for the defects showed the expression of the TCR ζ chain was attenuated, or absent in more than half of SLE patients. Moreover, the aberrant transcripts of the TCR ζ chain, including spliced variants lacking exon 7 and with a short 3′-UTR, were detected in SLE T-cells. Although attenuated expression of the TCR ζ chain is also observed in patients with cancers, infections, and other autoimmune diseases, sustained attenuation of TCR ζ expression and aberrant transcripts are only observed in SLE. In this review we discuss the unique features of the TCR ζ defects in SLE.
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