[Effects of altered IFNAR expression on CD4+ CD25+ treg cell dysfunction in patients with systemic lupus erythematosus].
OBJECTIVE
To explore the role of type I interferon (IFNalpha) on the function of CD4+ CD25+ regulatory T (Treg) cells in patients with systemic lupus erythematosus (SLE).


METHODS
Twenty patients with newly-onset active SLE and 20 healthy controls were recruited in this study. The expressions of type I interferon a receptor (IFNAR) on Treg cells were analyzed using flow cytometry. CD4+ CD25+ Treg cells were purified by magnetic-activated cell sorter (MACS). The function of these cells was assessed in vitro with or without IFNalpha (500 U/mL). The effect of exogenous IFNalpha on the apoptosis of Treg cells and the expression level of FOXP3, CTLA-4, and pAKT in Treg cells were analyzed using flow cytometry. Results The expression levels of IFNAR1 on CD4+ CD25+ Treg cells were significantly higher in the SLE patients than in the healthy controls (P=0.0006). There was a positive correlation between the expression levels of IFNAR on Treg cells and the SLEDAI scores in the SLE patients. Exogenous IFNalpha impaired the suppressive capacity of Treg cells in the SLE patients. However, neither the apoptosis of Treg cells nor the expression levels of FOXP3 and CTLA-4 on Treg cells were influenced by IFNalpha stimulation. IFNalpha enhanced AKT phosphorylation in Treg cells in the SLE patients.


CONCLUSIONS
Altered IFNAR expression may contribute to Treg cell dysfunction in SLE patients through enhancing AKT phosphorylation in Treg cells.
Yan
Y
He
Yun
Y
Peng
Chun-yu
CY
Tan
Yi
Y
Liu
Bing
B
Yan
D017209:Apoptosis; D060908:CTLA-4 Antigen / Q000378:metabolism; D016022:Case-Control Studies; D002469:Cell Separation; D002478:Cells, Cultured; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D008180:Lupus Erythematosus, Systemic / Q000503:physiopathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017471:Receptors, Interferon / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000473:pathology*
D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D016898:Interferon-alpha; D017471:Receptors, Interferon; D051057:Proto-Oncogene Proteins c-akt