Retagging Identifies Dendritic Cell-specific Intercellular Adhesion Molecule-3 (ICAM3)-grabbing Non-integrin (DC-SIGN) Protein as a Novel Receptor for a Major Allergen

Understanding of how allergic responses are selected and propagated is essential for developing novel therapies.Dendriticcells(DCs)havebeenshowntoplayakeyroleintheinitiation and maintenance of immune responses to microbialpathogens as well as to allergens, but the exact mechanisms oftheir involvement in allergic responses and Th2 cell differenti-ationhaveremainedelusive.Usingretagging,weidentifiedDC-SIGNasanovelreceptorinvolvedintheinitialrecognitionanduptake of the major house dust mite and dog allergens Der p 1andCanf1,respectively.Toconfirmthis,weusedgenesilencingto specifically inhibit DC-SIGN expression by DCs followed byallergenuptakestudies.BindinganduptakeofDerp1andCanf1allergenswasassessedbyELISAandflowcytometry.Intrigu-ingly, our data showed that silencing DC-SIGN on DCs pro-motesaTh2phenotypeinDC/Tcellco-cultures.Thesefindingsshould lead to better understanding of the molecular basis ofallergen-inducedTh2cellpolarizationandindoingsopavestheway for the rational design of novel intervention strategies bytargetingallergenreceptorsoninnateimmunecellsortheircar-bohydrate counterstructures on allergens.