How signaling and gene transcription aberrations dictate the systemic lupus erythematosus T cell phenotype.
T cells from patients with systemic lupus erythematosus (SLE) exhibit several discrete and specific defects that alter signaling pathways and, thus, the gene expression pattern and behavior upon stimulation. Rewiring of the CD3 complex and aggregation of surface-membrane lipid rafts grant SLE T cells a lower activation threshold and distort the ensuing signaling events. Additionally, increased expression of adhesion molecules within aggregated lipid rafts guides them to target organs. Aberrant cell signaling causes altered transcription factor expression and abnormal DNA-methylation patterns that lead to skewed gene expression. The result is an abnormally functioning T cell that exhibits several molecular alterations that can be exploited as therapeutic or diagnostic markers.
Crispín
José C
JC
Division of Rheumatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Kyttaris
Vasileios C
VC
Juang
Yuang-Taung
YT
Tsokos
George C
GC
D000818:Animals; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D008180:Lupus Erythematosus, Systemic / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D015398:Signal Transduction / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D014158:Transcription, Genetic / Q000276:immunology*