NKG2D ligand overexpression in lupus nephritis correlates with increased NK cell activity and differentiation in kidneys but not in the periphery

[摘要] NKcellsareamajorcomponentoftheimmunesystem,andalterationsintheiractivityarecorrelatedwithvariousautoimmunediseases.Inthepresentwork,weobservedanincreasedexpressionoftheNKG2DligandMICAinSLEpatients’kidneysbutnothealthysubjects.Wealsoshowglomerulus‐specificexpressionoftheNKG2DligandsRae‐1andMult‐1invariousmurineSLEmodels,whichcorrelatedwithahighernumberofglomerular‐infiltratingNKcells.AstheroleofNKcellsintheimmunopathogenesisofSLEispoorlyunderstood,weexploredNKcelldifferentiationandactivityintissuesandorgansinSLE‐pronemurinemodelsbyuseofdiseasedandprediseasedMRL/MpJandMRL/lprmice.WereportherethatphenotypicallyiNKcellsaccumulateonlyinthespleenbutnotinBMorkidneysofdiseasedmice.InfiltratingNKcellsinkidneysundergoingalupusnephriticprocessshowedamoremature,activatedphenotypecomparedwithkidney,aswellasperipheralNKcellsfromprediseasedmice,asdeterminedbyIFN‐γandSTAT5analysis.Thesefindingsandthepresenceofglomerulus‐specificNKG2Dligandsinlupus‐pronemiceidentifyaroleforNKcellsandNKG2Dligandsinthelupusnephriticprocess,whichcouldaidinunderstandingtheirroleinhumanSLE...

[学科分类] 生理学

[关键词] MICA;Rae;MRL/MpJ;MRL/lpr;T‐bet;Eomes