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Immune cell signaling in lupus
G C Tsokos1, H K Wong, E J Enyedy
1Department of Medicine, Uniformed Services University of the Health Sciences, and Walter Reed Army Institute of Research, Silver Spring, Maryland 20910-7500, USA. gtsokos@usa.net
Current Opinion in Rheumatology
|September 16, 2000
Summary
Lupus lymphocytes exhibit abnormal signaling, including increased calcium responses and altered gene activity. Understanding these molecular defects in T cell receptor zeta chain expression may lead to new lupus treatments.
Area of Science:
- Immunology
- Molecular Biology
- Autoimmune Diseases
Background:
- Lymphocyte fate is determined by antigen receptor, cytokine, and costimulatory molecule signals.
- Abnormal signaling in lupus lymphocytes includes increased calcium responses and protein hyperphosphorylation.
- Gene transcription is affected, with decreased nuclear factor kappaB (NFkappaB) activity.
Purpose of the Study:
- To investigate the molecular basis of abnormal lymphocyte signaling in lupus.
- To identify key molecular defects contributing to lupus pathogenesis.
Main Methods:
- Analysis of T cell receptor zeta chain expression.
- Assessment of Fc(epsilon)RI gamma chain and p65-Rel A protein levels.
- Evaluation of NFkappaB activity in lupus lymphocytes.
Main Results:
- Defective T cell receptor zeta chain expression observed.
- Overexpression of Fc(epsilon)RI gamma chain noted, acting as a zeta chain alternative.
- Decreased p65-Rel A protein levels, impacting inducible NFkappaB activity.
Conclusions:
- Molecular defects in T cell receptor signaling components underlie abnormal lupus lymphocyte function.
- These findings provide insights into lupus pathogenesis.
- Potential for developing targeted therapeutic interventions for lupus.