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Targeting of macrophage galactose-type C-type lectin (MGL) induces DC signaling and activation.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Napoletano, Chiara Zizzari, Ilaria Grazia Rughetti, Aurelia Rahimi, Hassan Akbari Irimura, Tatsuro Clausen, Henrik Wandall, Hans H. Belleudi, Francesca Bellati, Filippo Pierelli, Luca Frati, Luigi Nuti, Marianna |
| Copyright Year | 2012 |
| Abstract | Dendritic cells (DCs) sense the microenvironment through several types of receptors recognizing pathogen-associated molecular patterns. In particular, C-type lectins, expressed by distinct subsets of DCs, recognize and internalize specific carbohydrate antigen in a Ca(2+) -dependent manner. Targeting of these receptors is becoming an efficient strategy of delivering antigens in DC-based anticancer immunotherapy. Here we investigated the role of the macrophage galactose type C-lectin receptor (MGL), expressed by immature DCs (iDCs), as a molecular target for α-N-acetylgalactosamine (GalNAc or Tn)-carrying tumor-associated antigens to improve DC performance. MGL expressed by ex vivo-generated iDCs from healthy donors was engaged by a 60-mer MUC1(9Tn) -glycopeptide as a Tn-carrying tumor-associated antigen, and an anti-MGL antibody, as a specific MGL binder. We demonstrated that MGL engagement induced homotrimers and homodimers, triggering the phosphorylation of extracellular signal-regulated kinase 1,2 (ERK1,2) and nuclear factor-κB activation. Analysis of DC phenotype and function demonstrated that MGL engagement improved DC performance as antigen-presenting cells, promoting the upregulation of maturation markers, a decrease in phagocytosis, an enhancement of motility, and most importantly an increase in antigen-specific CD8(+) T-cell activation. These results demonstrate that the targeting of MGL receptor on human DCs has an adjuvant effect and that this strategy can be used to design novel anticancer vaccines. |
| File Format | PDF HTM / HTML |
| DOI | 10.1002/eji.201142086 |
| PubMed reference number | 22531918 |
| Journal | Medline |
| Volume Number | 42 |
| Issue Number | 4 |
| Alternate Webpage(s) | http://www.dendritics.net/files/documentation/Napoletano_N_et_al_,_125A10,_2012.pdf |
| Journal | European journal of immunology |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
