PMID- 22531918
OWN - NLM
STAT- MEDLINE
DCOM- 20120618
LR  - 20131121
IS  - 1521-4141 (Electronic)
IS  - 0014-2980 (Linking)
VI  - 42
IP  - 4
DP  - 2012 Apr
TI  - Targeting of macrophage galactose-type C-type lectin (MGL) induces DC signaling 
      and activation.
PG  - 936-45
LID - 10.1002/eji.201142086 [doi]
AB  - 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 alpha-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-kappaB 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.
CI  - (c) 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
FAU - Napoletano, Chiara
AU  - Napoletano C
AD  - Department of Experimental Medicine, Sapienza University, Rome, Italy.
FAU - Zizzari, Ilaria G
AU  - Zizzari IG
FAU - Rughetti, Aurelia
AU  - Rughetti A
FAU - Rahimi, Hassan
AU  - Rahimi H
FAU - Irimura, Tatsuro
AU  - Irimura T
FAU - Clausen, Henrik
AU  - Clausen H
FAU - Wandall, Hans H
AU  - Wandall HH
FAU - Belleudi, Francesca
AU  - Belleudi F
FAU - Bellati, Filippo
AU  - Bellati F
FAU - Pierelli, Luca
AU  - Pierelli L
FAU - Frati, Luigi
AU  - Frati L
FAU - Nuti, Marianna
AU  - Nuti M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Eur J Immunol
JT  - European journal of immunology
JID - 1273201
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Cancer Vaccines)
RN  - 0 (Lectins, C-Type)
RN  - 0 (MGL lectin, human)
RN  - 0 (MUC1 protein, human)
RN  - 0 (Mucin-1)
RN  - 0 (NF-kappa B)
RN  - EC 2.7.11.24 (MAPK1 protein, human)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - SY7Q814VUP (Calcium)
RN  - V956696549 (Acetylglucosamine)
SB  - IM
MH  - Acetylglucosamine/immunology/metabolism
MH  - Antigens, Neoplasm/immunology
MH  - CD8-Positive T-Lymphocytes/*immunology/metabolism
MH  - Calcium/immunology/metabolism
MH  - Cancer Vaccines/immunology
MH  - Cells, Cultured
MH  - Dendritic Cells/cytology/*immunology/metabolism
MH  - Humans
MH  - Lectins, C-Type/*immunology/metabolism
MH  - Lymphocyte Activation/*physiology
MH  - MAP Kinase Signaling System/*immunology
MH  - Mitogen-Activated Protein Kinase 1/immunology/metabolism
MH  - Mitogen-Activated Protein Kinase 3/immunology/metabolism
MH  - Mucin-1/immunology/metabolism
MH  - NF-kappa B/immunology/metabolism
MH  - Phosphorylation/immunology
MH  - Up-Regulation/immunology
EDAT- 2012/04/26 06:00
MHDA- 2012/06/19 06:00
CRDT- 2012/04/26 06:00
PHST- 2012/04/26 06:00 [entrez]
PHST- 2012/04/26 06:00 [pubmed]
PHST- 2012/06/19 06:00 [medline]
AID - 10.1002/eji.201142086 [doi]
PST - ppublish
SO  - Eur J Immunol. 2012 Apr;42(4):936-45. doi: 10.1002/eji.201142086.