PMID- 23762309
OWN - NLM
STAT- MEDLINE
DCOM- 20140114
LR  - 20240109
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 6
DP  - 2013
TI  - The role of the e3 ligase cbl-B in murine dendritic cells.
PG  - e65178
LID - 10.1371/journal.pone.0065178 [doi]
LID - e65178
AB  - Dendritic cells (DCs) are potent antigen-presenting cells with a promising 
      potential in cancer immunotherapy. Cbl proteins are E3 ubiquitin ligases and have 
      been implicated in regulating the functional activity of various immune cells. As 
      an example, c-Cbl negatively affects DC activation. We here describe that another 
      member of the Cbl-protein family (i.e. Cbl-b) is highly expressed in murine 
      bone-marrow-derived DCs (BMDCs). Differentiation of cblb-/- bone marrow 
      mononuclear cells into classical BMDCs is unaltered, except enhanced induction of 
      DEC-205 (CD205) expression. When tested in mixed-lymphocyte reaction (MLR), 
      cblb-/- BMDCs exhibit increased allo-stimulatory capacity in vitro. BMDCs were 
      next in vitro stimulated by various toll like receptor (TLR)-agonists (LPS, 
      Poly(I:C), CpG) and exposed to FITC-labeled dextran. Upon TLR-stimulation, 
      cblb-/- BMDCs produce higher levels of proinflammatory cytokines (IL-1alpha, IL-6 and 
      TNF-alpha) and exhibit a slightly higher level of FITC-dextran uptake. To further 
      characterize the functional significance of cblb-/- BMDCs we tested them in 
      antigen-specific T cell responses against ovalbumin (OVA) protein and peptides, 
      activating either CD8(+) OT-I or CD4(+) OT-II transgenic T cells. However, 
      cblb-/- BMDCs are equally effective in inducing antigen-specific T cell responses 
      when compared to wildtype BMDCs both in vitro and in vivo. The migratory capacity 
      into lymph nodes during inflammation was similarly not affected by the absence of 
      Cbl-b. In line with these observations, cblb-/- peptide-pulsed BMDCs are equally 
      effective vaccines against OVA-expressing B16 tumors in vivo when compared to 
      wildtype BMDCs. We conclude that in contrast to c-Cbl, Cbl-b plays only a limited 
      role in the induction of Ag-specific T cell responses by murine BMDCs in vitro 
      and in vivo.
FAU - Wallner, Stephanie
AU  - Wallner S
AD  - Laboratory of Tumor Immunology, Tyrolean Cancer Research Institute, Innsbruck, 
      Austria.
FAU - Lutz-Nicoladoni, Christina
AU  - Lutz-Nicoladoni C
FAU - Tripp, Christoph H
AU  - Tripp CH
FAU - Gastl, Gunther
AU  - Gastl G
FAU - Baier, Gottfried
AU  - Baier G
FAU - Penninger, Josef M
AU  - Penninger JM
FAU - Stoitzner, Patrizia
AU  - Stoitzner P
FAU - Wolf, Dominik
AU  - Wolf D
LA  - eng
GR  - P 25044/FWF_/Austrian Science Fund FWF/Austria
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130606
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Antigens, CD)
RN  - 0 (Cblb protein, mouse)
RN  - 0 (Cytokines)
RN  - 0 (DEC-205 receptor)
RN  - 0 (Dextrans)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Minor Histocompatibility Antigens)
RN  - 0 (Peptides)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (fluorescein isothiocyanate dextran)
RN  - 9006-59-1 (Ovalbumin)
RN  - EC 2.3.2.27 (Proto-Oncogene Proteins c-cbl)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - I223NX31W9 (Fluorescein-5-isothiocyanate)
RN  - O84C90HH2L (Poly I-C)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/deficiency/genetics/*immunology
MH  - Animals
MH  - Antigens, CD/genetics/immunology
MH  - Biological Transport
MH  - Bone Marrow Cells/cytology/drug effects/*immunology
MH  - CD4-Positive T-Lymphocytes/cytology/*immunology
MH  - CD8-Positive T-Lymphocytes/cytology/*immunology
MH  - Cell Differentiation
MH  - Cytokines/biosynthesis/immunology
MH  - Dendritic Cells/cytology/drug effects/*immunology
MH  - Dextrans/metabolism
MH  - Fluorescein-5-isothiocyanate/analogs & derivatives/metabolism
MH  - Gene Expression
MH  - Lectins, C-Type/genetics/immunology
MH  - Lipopolysaccharides/pharmacology
MH  - Lymphocyte Culture Test, Mixed
MH  - Melanoma, Experimental/drug therapy/immunology/pathology
MH  - Mice
MH  - Mice, Knockout
MH  - Minor Histocompatibility Antigens
MH  - Ovalbumin/immunology
MH  - Peptides/pharmacology
MH  - Poly I-C/pharmacology
MH  - Proto-Oncogene Proteins c-cbl/deficiency/genetics/*immunology
MH  - Receptors, Cell Surface/genetics/immunology
MH  - Skin Neoplasms/drug therapy/immunology/pathology
MH  - Ubiquitin-Protein Ligases/deficiency/genetics/*immunology
PMC - PMC3675148
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/06/14 06:00
MHDA- 2014/01/15 06:00
PMCR- 2013/06/06
CRDT- 2013/06/14 06:00
PHST- 2013/01/31 00:00 [received]
PHST- 2013/04/23 00:00 [accepted]
PHST- 2013/06/14 06:00 [entrez]
PHST- 2013/06/14 06:00 [pubmed]
PHST- 2014/01/15 06:00 [medline]
PHST- 2013/06/06 00:00 [pmc-release]
AID - PONE-D-13-05819 [pii]
AID - 10.1371/journal.pone.0065178 [doi]
PST - epublish
SO  - PLoS One. 2013 Jun 6;8(6):e65178. doi: 10.1371/journal.pone.0065178. Print 2013.