Defects in Notch1 upregulation upon activation of T Cells from patients with systemic lupus erythematosus are related to lupus disease activity

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by the production of autoantibodies and deposition of immune complexes in various organs. T cells play a central role in driving disease progression, and multiple defects in T cells from patients with SLE have been uncovered....

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Bibliographic Details
Published in:Lupus 2008-07, Vol.17 (7), p.645-653
Main Authors: Sodsai, P, Hirankarn, N, Avihingsanon, Y, Palaga, T
Format: Article
Language:English
Subjects:
Adolescent
Adult
Apoptosis
Autoimmune diseases
Cell Proliferation
Disease Progression
Drug dosages
Female
Forkhead Transcription Factors - genetics
Forkhead Transcription Factors - metabolism
Humans
Ligands
Lupus
Lupus Erythematosus, Systemic - immunology
Lupus Erythematosus, Systemic - pathology
Lupus Erythematosus, Systemic - physiopathology
Lymphocyte Activation - immunology
Lymphocytes
Medicine
Receptor, Notch1 - genetics
Receptor, Notch1 - metabolism
Remission (Medicine)
Signal Transduction
T-Lymphocytes - immunology
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Summary:Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by the production of autoantibodies and deposition of immune complexes in various organs. T cells play a central role in driving disease progression, and multiple defects in T cells from patients with SLE have been uncovered. Notch signalling is an evolutionarily well-conserved signalling cascade involved in the proliferation, differentiation and apoptosis of T lymphocytes during development and peripheral effector functions. In this study, we investigated the correlation between expression of Notch receptor and the severity of SLE disease. On the contrary to T lymphocytes from healthy controls (n = 11), Tlymphocytes from patients with active SLE (n = 12) failed to upregulate Notch1 upon in-vitro stimulation as quantified by quantitative real time RT-PCR (P ≤ 0.025). Among patients with inactive SLE (n = 10), those with late onset of flare exhibited significantly less Notch1 upregulation compared with SLE patients with remission. Expression of the Notch target genes, Hes1 and deltex, was also lower in patients with active SLE. The decrease in Notch1 mRNA expression was consistent with less Notch1 protein expression in patients with active SLE. The defects in Notch1 upregulation correlated with decreased proliferation, CD25 and Foxp3 expression upon stimulation in vitro. Taken together, the failure of T cells to upregulate Notch1 upon activation may be a key feature of active SLE and a potential therapeutic target.
ISSN:0961-2033
1477-0962
DOI:10.1177/0961203308089406