Abnormalities of T cell signaling in systemic lupus erythematosus - PubMed (original) (raw)

Review

Abnormalities of T cell signaling in systemic lupus erythematosus

Vaishali R Moulton et al. Arthritis Res Ther. 2011.

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.

PubMed Disclaimer

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 _CD3_ζ 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.

Similar articles

Cited by

References

    1. Jury EC, Kabouridis PS, Abba A, Mageed RA, Isenberg DA. Increased ubiquitination and reduced expression of LCK in T lymphocytes from patients with systemic lupus erythematosus. Arthritis Rheum. 2003;48:1343–1354. doi: 10.1002/art.10978. - DOI - PubMed
    1. Jury EC, Kabouridis PS, Flores-Borja F, Mageed RA, Isenberg DA. Altered lipid raft-associated signaling and ganglioside expression in T lymphocytes from patients with systemic lupus erythematosus. J Clin Invest. 2004;113:1176–1187. - PMC - PubMed
    1. Krishnan S, Nambiar MP, Warke VG, Fisher CU, Mitchell J, Delaney N, Tsokos GC. Alterations in lipid raft composition and dynamics contribute to abnormal T cell responses in systemic lupus erythematosus. J Immunol. 2004;172:7821–7831. - PubMed
    1. Kabouridis PS, Jury EC. Lipid rafts and T-lymphocyte function: implications for autoimmunity. FEBS Lett. 2008;582:3711–3718. doi: 10.1016/j.febslet.2008.10.006. - DOI - PMC - PubMed
    1. Liu MF, Liu HS, Wang CR, Lei HY. Expression of CTLA-4 molecule in peripheral blood T lymphocytes from patients with systemic lupus erythematosus. J Clin Immunol. 1998;18:392–398. doi: 10.1023/A:1023226621966. - DOI - PubMed

Publication types

MeSH terms

LinkOut - more resources