An essential role of interleukin‐17 receptor signaling in the development of autoimmune glomerulonephritis

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: IL‐;    17;    inflammation;    kidney;   

DOI  :  10.1189/jlb.3A0414-184R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Inrecentyears,proinflammatorycytokinesinthenephritickidneyappeartocontributetothepathogenesisofAGN.Thecomplexinflammatorycytokinenetworkthatdrivesrenalpathologyispoorlyunderstood.IL‐17,thesignaturecytokineofTh17cells,whichpromotesautoimmunepathologyinavarietyofsettings,isbeginningtobeidentifiedinacuteandchronickidneydiseasesaswell.However,theroleofIL‐17‐mediatedrenaldamageinthenephritickidneyhasnotbeenelucidated.Here,withtheuseofamurinemodelofexperimentalAGN,weshowedthatIL‐17RAsignalingiscriticalforthedevelopmentofrenalpathology.Despitenormalsystemicautoantibodyresponseandglomerularimmune‐complexdeposition,IL‐17RA−/−miceexhibitadiminishedinfluxofinflammatorycellsandkidney‐specificexpressionofIL‐17targetgenescorrelatingwithdiseaseresistanceinAGN.IL‐17enhancedtheproductionofproinflammatorycytokinesandchemokinesfromtECs.Finally,wewereabletoshowthatneutralizationofIL‐17AamelioratedrenalpathologyinWTmicefollowingAGN.TheseresultsclearlydemonstratedthatIL‐17RAsignalingsignificantlycontributestorenaltissueinjuryinexperimentalAGNandsuggestthatblockingIL‐17RAmaybeapromisingtherapeuticstrategyforthetreatmentofproliferativeandcrescenticglomerulonephritis...

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