Therapeutic targets of misguided T cells in systemic lupus erythematosus.
It is widely accepted that T cells with defective function play a central role in the pathogenesis of systemic lupus erythematosus (SLE). The detailed molecular mechanism underlying the aberrant function of SLE T cells is now being revealed. The TCR zeta chain, transcription factor, elf-1, inflammation signal transducer NF-kB, and PKC theta have been identified as the responsible molecules. In contrast to the defective signal transduction molecules, surface structures such as adhesion molecules, and co-stimulators have been reported to increase in their expression and function. Glucocorticoids and immunosuppressive agents have greatly improved the outcome of acute diseases and 5-year survival rate. However, it is suggested that long-term survival and quality of life appears to be unsatisfactory. Although the medical management of SLE is not sufficient to warrant long-term survival of young patients, recent progress in anti-cytokine biologics therapy against rheumatoid arthritis (RA) has facilitated searching for the molecular targets of SLE. In this report, we briefly review the molecular basis of SLE pathogenesis, and discuss possible therapeutic targets in this disease, focusing particularly on signal transduction and adhesion molecules in T cells.
Takeuchi
Tsutomu
T
Second Department of Internal Medicine, Saitama Medical Center, Saitama Medical School, Kamoda 1981, Kawagoe, Saitama 350-8550, Japan. tsutake@saitama-med.ac.jp
Tsuzaka
Kensei
K
Kameda
Hideto
H
Amano
Kouichi
K
D000818:Animals; D002448:Cell Adhesion; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000503:physiopathology; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000502:physiology
D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7