PMID- 26921214
OWN - NLM
STAT- MEDLINE
DCOM- 20171101
LR  - 20171109
IS  - 1460-2377 (Electronic)
IS  - 0953-8178 (Linking)
VI  - 28
IP  - 10
DP  - 2016 Oct
TI  - A novel role of MMP-13 for murine DC function: its inhibition dampens T-cell 
      activation.
PG  - 473-487
AB  - Dendritic cells (DCs) have been shown to express matrix metalloproteinase 13 
      (MMP-13), but little is known about its specific function in DCs and its role in 
      inflammatory conditions. In the present study, we describe a novel role of MMP-13 
      in regulating the immunostimulatory function of murine DCs through moderating 
      MHC-I surface presentation, endocytosis and cytokine/chemokine secretion. MMP-13 
      expression was confirmed in bone marrow-derived DCs at both the mRNA and the 
      protein level and, furthermore, at the activity level. Remarkably, LPS treatment 
      strongly enhanced MMP-13 mRNA expression as well as MMP-13 activity, indicating 
      an important role of MMP-13 in inflammatory processes. Functionally, MMP-13 
      inhibition did not influence the DC migratory capacity, while endocytosis of 
      ovalbumin was significantly decreased. Inhibition of MMP-13 lowered the 
      capability of murine DCs to activate CD8(+) T cells, apparently through reducing 
      MHC-I surface presentation. Decreased surface expression of CD11c on DCs, as well 
      as changes in the DC cytokine/chemokine profile after MMP-13 inhibition, 
      emphasizes the influence of MMP-13 on DC function. Moreover, T-cell-targeting 
      cytokines such as IL-12, IL-23 and IL-6 were significantly reduced. Collectively, 
      our data reveal a novel involvement of MMP-13 in regulating DC immunobiology 
      through moderating MHC-I surface presentation, endocytosis and cytokine/chemokine 
      secretion. Furthermore, the reduced MHC-I surface presentation by DCs resulted in 
      a poor CD8(+) T-cell response in vitro This novel finding indicates that MMP-13 
      might be a promising target for therapeutic intervention in inflammatory 
      diseases.
CI  - (c) The Japanese Society for Immunology. 2016. All rights reserved. For 
      permissions, please e-mail: journals.permissions@oup.com.
FAU - Bartmann, Juliane
AU  - Bartmann J
AD  - Comprehensive Pneumology Center, University Hospital of the 
      Ludwig-Maximilians-University Munich, Asklepios Kliniken Gauting and Helmholtz 
      Zentrum Munchen, Member of the German Center for Lung Research, 81377 Munich, 
      Germany.
FAU - Frankenberger, Marion
AU  - Frankenberger M
AD  - Comprehensive Pneumology Center, University Hospital of the 
      Ludwig-Maximilians-University Munich, Asklepios Kliniken Gauting and Helmholtz 
      Zentrum Munchen, Member of the German Center for Lung Research, 81377 Munich, 
      Germany.
FAU - Neurohr, Claus
AU  - Neurohr C
AD  - Comprehensive Pneumology Center, University Hospital of the 
      Ludwig-Maximilians-University Munich, Asklepios Kliniken Gauting and Helmholtz 
      Zentrum Munchen, Member of the German Center for Lung Research, 81377 Munich, 
      Germany Department of Pneumology, Klinikum der Universitat Munchen-Grosshadern, 
      81377 Munich, Germany.
FAU - Eickelberg, Oliver
AU  - Eickelberg O
AD  - Comprehensive Pneumology Center, University Hospital of the 
      Ludwig-Maximilians-University Munich, Asklepios Kliniken Gauting and Helmholtz 
      Zentrum Munchen, Member of the German Center for Lung Research, 81377 Munich, 
      Germany.
FAU - Noessner, Elfriede
AU  - Noessner E
AD  - Institute of Molecular Immunology, Helmholtz Zentrum Munchen, 81377 Munich, 
      Germany.
FAU - von Wulffen, Werner
AU  - von Wulffen W
AD  - Comprehensive Pneumology Center, University Hospital of the 
      Ludwig-Maximilians-University Munich, Asklepios Kliniken Gauting and Helmholtz 
      Zentrum Munchen, Member of the German Center for Lung Research, 81377 Munich, 
      Germany Department of Respiratory Diseases, Klinik Augustinum Munchen, 81375 
      Munich, Germany wulffen@med.augustinum.de.
LA  - eng
PT  - Journal Article
DEP - 20160226
PL  - England
TA  - Int Immunol
JT  - International immunology
JID - 8916182
RN  - 0 (Matrix Metalloproteinase Inhibitors)
RN  - 0 (RNA, Messenger)
RN  - EC 3.4.24.- (Matrix Metalloproteinase 13)
SB  - IM
MH  - Animals
MH  - CD8-Positive T-Lymphocytes/cytology/drug effects/*immunology
MH  - Dendritic Cells/drug effects/*enzymology/*immunology
MH  - Female
MH  - Inflammation/immunology
MH  - Lymphocyte Activation/*drug effects
MH  - Matrix Metalloproteinase 13/genetics/*metabolism
MH  - Matrix Metalloproteinase Inhibitors/*pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - RNA, Messenger/genetics/metabolism
OTO - NOTNLM
OT  - CD8+ T-cell activation
OT  - DCs
OT  - MHC-I
OT  - MMP-13
OT  - cytokine profile
OT  - endocytosis
EDAT- 2016/02/28 06:00
MHDA- 2017/11/02 06:00
CRDT- 2016/02/28 06:00
PHST- 2014/12/19 00:00 [received]
PHST- 2016/02/19 00:00 [accepted]
PHST- 2016/02/28 06:00 [pubmed]
PHST- 2017/11/02 06:00 [medline]
PHST- 2016/02/28 06:00 [entrez]
AID - dxw008 [pii]
AID - 10.1093/intimm/dxw008 [doi]
PST - ppublish
SO  - Int Immunol. 2016 Oct;28(10):473-487. doi: 10.1093/intimm/dxw008. Epub 2016 Feb 
      26.