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Targeting of macrophage galactose‐type C ‐type lectin ( MGL ) induces DC signaling and activation
Author(s) -
Napoletano Chiara,
Zizzari Ilaria G.,
Rughetti Aurelia,
Rahimi Hassan,
Irimura Tatsuro,
Clausen Henrik,
Wandall Hans H.,
Belleudi Francesca,
Bellati Filippo,
Pierelli Luca,
Frati Luigi,
Nuti Marianna
Publication year - 2012
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.201142086
Subject(s) - c type lectin , biology , antigen , microbiology and biotechnology , receptor , lectin , t cell , downregulation and upregulation , immunology , immune system , biochemistry , gene
Dendritic cells ( DC s) sense the microenvironment through several types of receptors recognizing pathogen‐associated molecular patterns. In particular, C ‐type lectins, expressed by distinct subsets of DC s, 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 DC s (iDCs), as a molecular target for α‐N‐acetylgalactosamine ( G al NA c or T n)‐carrying tumor‐associated antigens to improve DC performance. MGL expressed by ex vivo‐generated i DC s from healthy donors was engaged by a 60‐mer MUC 1 9 T n ‐glycopeptide as a T n‐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 ( ERK 1,2) 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 CD 8 + 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.