Abnormalities of T cell signaling in systemic lupus erythematosus

Vaishali R Moulton, George C Tsokos, Vaishali R Moulton, George C Tsokos

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease resulting from a loss of tolerance to multiple self antigens, and characterized by autoantibody production and inflammatory cell infiltration in target organs, such as the kidneys and brain. T cells are critical players in SLE pathophysiology as they regulate B cell responses and also infiltrate target tissues, leading to tissue damage. Abnormal signaling events link to defective gene transcription and altered cytokine production, contributing to the aberrant phenotype of T cells in SLE. Study of signaling and gene transcription abnormalities in SLE T cells has led to the identification of novel targets for therapy.

Figures

Figure 1
Figure 1
Schematic showing the T cell receptor signaling architecture in normal and systemic lupus erythematosus T cells. SLE, systemic lupus erythematosus; TCR, T cell receptor.
Figure 2
Figure 2
Schematic showing transcription factors involved in IL2 production in T cells. AP1, activated protein 1; CAMKIV, calcium/calmodulin-dependent kinase IV; CREB, cAMP response element-binding; CREM, cAMP response element modulator; MAPK, mitogen-activated protein kinase; NFAT, nuclear factor of activated T cells; PKC, protein kinase C; PP, protein phosphatase.
Figure 3
Figure 3
Schematic showing the CD3ζ gene. Genomic DNA with eight exons (top), the mRNA with a full-length 906-bp 3' UTR (WT; middle) and the 344-bp alternatively spliced (AS) 3' UTR variant (bottom). SLE T cells express increased amounts of the unstable AS splice variant relative to the stable WT isoform.

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