PMID- 29235514
OWN - NLM
STAT- MEDLINE
DCOM- 20190813
LR  - 20231213
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
IP  - 1
DP  - 2017 Dec 13
TI  - Substrate stiffness influences phenotype and function of human antigen-presenting 
      dendritic cells.
PG  - 17511
LID - 10.1038/s41598-017-17787-z [doi]
LID - 17511
AB  - Dendritic cells (DCs) are specialized immune cells that scan peripheral tissues 
      for foreign material or aberrant cells and, upon recognition of such danger 
      signals, travel to lymph nodes to activate T cells and evoke an immune response. 
      For this, DCs travel large distances through the body, encountering a variety of 
      microenvironments with different mechanical properties such as tissue stiffness. 
      While immune-related pathological conditions such as fibrosis or cancer are 
      associated with tissue stiffening, the role of tissue stiffness in regulating key 
      functions of DCs has not been studied yet. Here, we investigated the effect of 
      substrate stiffness on the phenotype and function of DCs by conditioning DCs on 
      polyacrylamide substrates of 2, 12 and 50 kPa. Interestingly, we found that 
      C-type lectin expression on immature DCs (iDCs) is regulated by substrate 
      stiffness, resulting in differential antigen internalization. Furthermore, we 
      show that substrate stiffness affects beta(2) integrin expression and podosome 
      formation by iDCs. Finally, we demonstrate that substrate stiffness influences 
      CD83 and CCR7 expression on mature DCs, the latter leading to altered 
      chemokine-directed migration. Together, our results indicate that DC phenotype 
      and function are affected by substrate stiffness, suggesting that tissue 
      stiffness is an important determinant for modulating immune responses.
FAU - Mennens, Svenja F B
AU  - Mennens SFB
AUID- ORCID: 0000-0003-1099-2894
AD  - Department of Cell Biology, Radboud Institute for Molecular Life Sciences, 
      Radboud University Medical Center, Geert Grooteplein Zuid 26-28, 6525 GA, 
      Nijmegen, The Netherlands.
FAU - Bolomini-Vittori, Matteo
AU  - Bolomini-Vittori M
AD  - Department of Cell Biology, Radboud Institute for Molecular Life Sciences, 
      Radboud University Medical Center, Geert Grooteplein Zuid 26-28, 6525 GA, 
      Nijmegen, The Netherlands.
FAU - Weiden, Jorieke
AU  - Weiden J
AUID- ORCID: 0000-0002-2485-0590
AD  - Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, 
      Radboud University Medical Center, Geert Grooteplein Zuid 26-28, 6525 GA, 
      Nijmegen, The Netherlands.
FAU - Joosten, Ben
AU  - Joosten B
AD  - Department of Cell Biology, Radboud Institute for Molecular Life Sciences, 
      Radboud University Medical Center, Geert Grooteplein Zuid 26-28, 6525 GA, 
      Nijmegen, The Netherlands.
FAU - Cambi, Alessandra
AU  - Cambi A
AUID- ORCID: 0000-0003-1597-1582
AD  - Department of Cell Biology, Radboud Institute for Molecular Life Sciences, 
      Radboud University Medical Center, Geert Grooteplein Zuid 26-28, 6525 GA, 
      Nijmegen, The Netherlands. Alessandra.Cambi@radboudumc.nl.
FAU - van den Dries, Koen
AU  - van den Dries K
AD  - Department of Cell Biology, Radboud Institute for Molecular Life Sciences, 
      Radboud University Medical Center, Geert Grooteplein Zuid 26-28, 6525 GA, 
      Nijmegen, The Netherlands. Koen.vandenDries@radboudumc.nl.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20171213
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Acrylic Resins)
RN  - 0 (Antigens, CD)
RN  - 0 (CCR7 protein, human)
RN  - 0 (CD18 Antigens)
RN  - 0 (Immunoglobulins)
RN  - 0 (Lectins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Receptors, CCR7)
RN  - 9003-05-8 (polyacrylamide)
MH  - Acrylic Resins
MH  - Antigens, CD/metabolism
MH  - CD18 Antigens/metabolism
MH  - Cell Adhesion/physiology
MH  - Cell Movement/physiology
MH  - Cell Survival
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Dendritic Cells/*physiology
MH  - Elasticity
MH  - Humans
MH  - Immunoglobulins/metabolism
MH  - Lectins/metabolism
MH  - Membrane Glycoproteins/metabolism
MH  - Podosomes/metabolism
MH  - Receptors, CCR7/metabolism
MH  - T-Lymphocytes/physiology
MH  - *Tissue Scaffolds
MH  - CD83 Antigen
PMC - PMC5727489
COIS- The authors declare that they have no competing interests.
EDAT- 2017/12/14 06:00
MHDA- 2019/08/14 06:00
PMCR- 2017/12/13
CRDT- 2017/12/14 06:00
PHST- 2017/08/11 00:00 [received]
PHST- 2017/11/30 00:00 [accepted]
PHST- 2017/12/14 06:00 [entrez]
PHST- 2017/12/14 06:00 [pubmed]
PHST- 2019/08/14 06:00 [medline]
PHST- 2017/12/13 00:00 [pmc-release]
AID - 10.1038/s41598-017-17787-z [pii]
AID - 17787 [pii]
AID - 10.1038/s41598-017-17787-z [doi]
PST - epublish
SO  - Sci Rep. 2017 Dec 13;7(1):17511. doi: 10.1038/s41598-017-17787-z.