Chemokine decoy receptor D6 mimicking trap (D6MT) prevents allosensitization and immune rejection in murine corneal allograft model

摘要

Althoughcornealallotransplantationisperformedintheimmune‐privilegedcornea,manygraftsarestillrejectedaftertransplantation.ThisstudyexaminedtheroleofchemokinereceptorD6expressioninacornealallograftrejection,investigatedthemodulationofD6expressionincells,anddeterminedtheeffectofD6ongraftsurvival.Interestingly,D6washighlyexpressedinCD45?cellsandthecornealepitheliumofacceptedcornealallografts.Fromthemousecornealallograftmodel,TGF‐βwasfoundtoplayakeyroleinD6up‐regulation,leadingtoreducedCCL2,CCL5,andCCL3.TomodulateD6chemokinebinding,aD6MTwasdevelopedandshowedeffectivechemokinetrappingthroughSPRandFACSassays.BytreatingcornealallograftswithD6MT,theallograftsurvivalratewasimproved,and(lymph)angiogenesiswasreduced.DirectallosensitizationandDCLNhomingwasdrasticallyreducedinthemousecornealallograftmodel.ThesefindingssuggestthatTGF‐βisapositiveregulatorofD6expression,anditisapotentialtherapeutictargettoenhancethesurvivalofcornealallografts...