PMID- 22205703 OWN - NLM STAT- MEDLINE DCOM- 20120409 LR - 20211021 IS - 1083-351X (Electronic) IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 287 IP - 8 DP - 2012 Feb 17 TI - Retagging identifies dendritic cell-specific intercellular adhesion molecule-3 (ICAM3)-grabbing non-integrin (DC-SIGN) protein as a novel receptor for a major allergen from house dust mite. PG - 5756-63 LID - 10.1074/jbc.M111.312520 [doi] AB - Dendritic cells (DCs) have been shown to play a key role in the initiation and maintenance of immune responses to microbial pathogens as well as to allergens, but the exact mechanisms of their involvement in allergic responses and Th2 cell differentiation have remained elusive. Using retagging, we identified DC-SIGN as a novel receptor involved in the initial recognition and uptake of the major house dust mite and dog allergens Der p 1 and Can f 1, respectively. To confirm this, we used gene silencing to specifically inhibit DC-SIGN expression by DCs followed by allergen uptake studies. Binding and uptake of Der p 1 and Can f 1 allergens was assessed by ELISA and flow cytometry. Intriguingly, our data showed that silencing DC-SIGN on DCs promotes a Th2 phenotype in DC/T cell co-cultures. These findings should lead to better understanding of the molecular basis of allergen-induced Th2 cell polarization and in doing so paves the way for the rational design of novel intervention strategies by targeting allergen receptors on innate immune cells or their carbohydrate counterstructures on allergens. FAU - Emara, Mohamed AU - Emara M AD - School of Molecular Medical Sciences, Queen's Medical Centre, The University of Nottingham, Nottingham NG7 2UH, United Kingdom. FAU - Royer, Pierre-Joseph AU - Royer PJ FAU - Mahdavi, Jafar AU - Mahdavi J FAU - Shakib, Farouk AU - Shakib F FAU - Ghaemmaghami, Amir M AU - Ghaemmaghami AM LA - eng GR - Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20111228 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Allergens) RN - 0 (Antigens, CD) RN - 0 (Antigens, Dermatophagoides) RN - 0 (Arthropod Proteins) RN - 0 (Cell Adhesion Molecules) RN - 0 (DC-specific ICAM-3 grabbing nonintegrin) RN - 0 (ICAM3 protein, human) RN - 0 (Lectins, C-Type) RN - 0 (Receptors, Cell Surface) RN - 0 (allergen Can f I) RN - EC 3.4.22.- (Cysteine Endopeptidases) RN - EC 3.4.22.- (Dermatophagoides pteronyssinus antigen p 1) SB - IM MH - Allergens/immunology/metabolism MH - Animals MH - Antigens, CD/*metabolism MH - Antigens, Dermatophagoides/immunology/*metabolism MH - Arthropod Proteins/immunology/*metabolism MH - Biological Transport/drug effects/immunology MH - Cell Adhesion Molecules/chemistry/*metabolism/pharmacology MH - Coculture Techniques MH - Cysteine Endopeptidases/immunology/*metabolism MH - Dendritic Cells/cytology/drug effects/immunology/*metabolism MH - Dogs MH - Dose-Response Relationship, Drug MH - Down-Regulation/drug effects MH - Humans MH - Lectins, C-Type/chemistry/*metabolism MH - Mice MH - NIH 3T3 Cells MH - Protein Binding MH - Pyroglyphidae/*immunology MH - Receptors, Cell Surface/chemistry/*metabolism MH - Solubility MH - Staining and Labeling MH - Th2 Cells/cytology/drug effects/immunology/metabolism PMC - PMC3285347 EDAT- 2011/12/30 06:00 MHDA- 2012/04/10 06:00 PMCR- 2011/12/28 CRDT- 2011/12/30 06:00 PHST- 2011/12/30 06:00 [entrez] PHST- 2011/12/30 06:00 [pubmed] PHST- 2012/04/10 06:00 [medline] PHST- 2011/12/28 00:00 [pmc-release] AID - S0021-9258(20)61232-7 [pii] AID - M111.312520 [pii] AID - 10.1074/jbc.M111.312520 [doi] PST - ppublish SO - J Biol Chem. 2012 Feb 17;287(8):5756-63. doi: 10.1074/jbc.M111.312520. Epub 2011 Dec 28.