Immune cell signaling in lupus.
The fate of the lymphocyte is determined by integration of signals delivered after the binding of antigen to the surface antigen receptor, signals delivered by cytokines that bind to their surface receptors, and signals initiated after the engagement of other surface receptors, known as costimulatory molecules. The summation of this input determines whether the immune cell will become stimulated, ignore the signal (anergy), or die (apoptosis). Antigen-receptor signaling events are abnormal in lupus lymphocytes, manifested by increased calcium responses and hyperphosphorylation of several cytosolic protein substrates. Further down, at the gene transcription level, the activity of the nuclear factor kappaB is decreased. These events are underwritten by defective T cell receptor zeta chain expression, overexpression of the gamma chain of the Fc(epsilon)RI that functions as an alternate of zeta chain, and decreased p65 -Rel A protein that is responsible for the inducible NFkappaB activity. Accumulated research data have enabled us to begin deciphering the molecular basis of the abnormal lupus lymphocyte and may lead to the development of new medicinal treatments for lupus.
Tsokos
G C
GC
Department 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
Wong
H K
HK
Enyedy
E J
EJ
Nambiar
M P
MP
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology; D002453:Cell Cycle; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D004967:Estrogens / Q000502:physiology; D005802:Genes, MHC Class II / Q000502:physiology; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology* / Q000503:physiopathology; D051379:Mice; D016328:NF-kappa B / Q000502:physiology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000172:deficiency / Q000235:genetics; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000502:physiology
D004967:Estrogens; D016328:NF-kappa B; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018808:Transcription Factor AP-1; D018844:Cyclin-Dependent Kinases