Down-Regulated NOD2 by Immunosuppressants in Peripheral Blood Cells in Patients with SLE Reduces the Muramyl Dipeptide-Induced IL-10 Production 英文参考文献.docVIP

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Down-Regulated NOD2 by Immunosuppressants in Peripheral Blood Cells in Patients with SLE Reduces the Muramyl Dipeptide-Induced IL-10 Production 英文参考文献.doc

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Down-Regulated NOD2 by Immunosuppressants in Peripheral Blood Cells in Patients with SLE Reduces the Muramyl Dipeptide-Induced IL-10 Production 英文参考文献

Down-RegulatedNOD2byImmunosuppressantsin PeripheralBloodCellsinPatientswithSLEReducesthe MuramylDipeptide-InducedIL-10Production Shui-LianYu1,Chun-KwokWong2,PurpleTsz-YanWong2,Da-PengChen2,3,Cheuk-ChunSzeto1, EdmundK.Li1,Lai-ShanTam1* 1DepartmentofMedicineandTherapeutics,PrinceofWalesHospital,TheChineseUniversityofHongKong,HongKong,China,2DepartmentofChemicalPathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China, 3Department of Clinical Laboratory, Children’s Hospital of Chongqing Medical University,Chongqing,China Abstract Background:Patternrecognitionreceptors(PRRs)suchasToll-likereceptorsareaberrantlyexpressedofperipheralblood mononuclearcells(PBMCs)insystemiclupuserythematosus(SLE)patients,forplayingimmunopathologicalroles. Methodology/Principal Findings: We investigated the expression and function of the PRR nucleotide-binding oligomerizationdomain(NOD2)inSLE.NOD2expressioninT,Blymphocytes,monocytes,myeloiddendriticcells(mDCs) and plasmacytoid dendritic cells (pDCs) was assessed in SLE patients and healthy controls (HCs) using flow cytometric analysis. Ex vivo production of cytokines from PBMCs upon NOD2 agonist muramyl dipeptide (MDP) stimulation was assessedusingCytometricBeadArray.Over-expressionofNOD2inmonocyteswasobservedinimmunosuppressantna?¨ve SLEpatients,andwaspositivelyassociatedwithlongerdiseaseduration.Immunosuppressivetherapywasanindependent explanatoryvariablefordownregulatingNOD2expressioninCD8+T,monocytes,mDCsandpDCs.Exvivobasalproductions ofcytokines(IL-6,IL-8andIL-10)weresignificantlyincreasedinimmunosuppressantna?¨vepatientsandpatientswithactive diseasedespiteimmunosuppressantscomparedwithHCs.UponMDPstimulaiton,relativeinduction(%)ofcytokines(IL-1b) fromPBMCwassignificantlyincreasedinimmunosuppressantna?¨vepatientswithinactivedisease,andpatientswithactive disease despite immunosuppressant treatment compared with HCs. Immunosuppressant usage was associated with a decreased basal production andMDP induce