Background and aims Systemic Lupus Erythematosus(SLE) is a prototype of autoimmune disease.Decreased cell numbers and suppressive defects of naturally occurring CD4+CD25+FOXP3 +regulatory T cells(Tregs) play an important role in the breakdown of SLE immune tolenrance.We have peviously observed significantly increased apoptosis of peripheral blood CD4+T cells in SLE patients.Our objective here was to detect the apoptosis of Tregs in SLE patients to see if it could contribute to reduced suppressive activity of Tregs,and further elucidate the genes and signalling pathways which trigger the apoptosis in these cells.
Methods The cell number and apoptosis rates of Tregs was respectively evaluated in SLE patients and normal controls(NCs) by FACS.The suppressive activity of Tregs was measured by coculture with CD4+CD25-CD127dim/-T cells.The relationship of abnormal Tregs apoptosis with clinical parameters was analysed by correlation analysis.Gene expression profiles of unstimulated Tregs from active SLE patients and NCs were generated by microarray analysis.Differential genes expression were verified by real time-PCR.
Results Tregs from SLE patients showed a significantly reduced number,elevated apoptosis rates and impared suppressive capacity compared with NCs.The increased Tregs apoptosis was negatively correlated with the total number of Tregs and positively correlated with disease activities.Microarray profiles of Tregs from SLE subjects reveal a cellular response that could make the cells sensitive to apoptosis,partially due to the stress responses,DNA-damaging and cytokine stimulation.
Conclusions This global picture of pathway-specific expression signatures is a step further dissecting Treg cells defects in the pathogenesis of SLE,and may shed light on the newly therapeutic strategies towards the aberrant Tregs apoptosis and reconstruction of SLE immune homeostasis.
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