PMID- 20111715
OWN - NLM
STAT- MEDLINE
DCOM- 20100520
LR  - 20211020
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 5
IP  - 1
DP  - 2010 Jan 27
TI  - Phospholipase C gamma 2 is critical for development of a murine model of 
      inflammatory arthritis by affecting actin dynamics in dendritic cells.
PG  - e8909
LID - 10.1371/journal.pone.0008909 [doi]
LID - e8909
AB  - BACKGROUND: Dendritic cells (DCs) are highly specialized cells, which capture 
      antigen in peripheral tissues and migrate to lymph nodes, where they dynamically 
      interact with and activate T cells. Both migration and formation of DC-T cell 
      contacts depend on cytoskeleton plasticity. However, the molecular bases 
      governing these events have not been completely defined. METHODOLOGY/PRINCIPAL 
      FINDINGS: Utilizing a T cell-dependent model of arthritis, we find that 
      PLCgamma2-/- mice are protected from local inflammation and bone erosion. 
      PLCgamma2 controls actin remodeling in dendritic cells, thereby affecting their 
      capacity to prime T cells. DCs from PLCgamma2-/- mice mature normally, however 
      they lack podosomes, typical actin structures of motile cells. Absence of 
      PLCgamma2 impacts both DC trafficking to the lymph nodes and migration towards 
      CCL21. The interaction with T cells is also affected by PLCgamma2 deficiency. 
      Mechanistically, PLCgamma2 is activated by CCL21 and modulates Rac activation. 
      Rac1/2-/- DCs also lack podosomes and do not respond to CCL21. Finally, antigen 
      pulsed PLCgamma2-/- DCs fail to promote T cell activation and induce inflammation 
      in vivo when injected into WT mice. Conversely, injection of WT DCs into 
      PLCgamma2-/- mice rescues the inflammatory response but not focal osteolysis, 
      confirming the importance of PLCgamma2 both in immune and bone systems. 
      CONCLUSIONS/SIGNIFICANCE: This study demonstrates a critical role for PLCgamma2 
      in eliciting inflammatory responses by regulating actin dynamics in DCs and 
      positions the PLCgamma2 pathway as a common orchestrator of bone and immune cell 
      functions during arthritis.
FAU - Cremasco, Viviana
AU  - Cremasco V
AD  - Department of Orthopaedics, Washington University School of Medicine, St. Louis, 
      Missouri, United States of America.
FAU - Benasciutti, Elisa
AU  - Benasciutti E
FAU - Cella, Marina
AU  - Cella M
FAU - Kisseleva, Marina
AU  - Kisseleva M
FAU - Croke, Monica
AU  - Croke M
FAU - Faccio, Roberta
AU  - Faccio R
LA  - eng
GR  - P30 AR057235/AR/NIAMS NIH HHS/United States
GR  - R01 AR053628/AR/NIAMS NIH HHS/United States
GR  - 63181/PHS HHS/United States
GR  - R01 AR52921/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, American Recovery and Reinvestment Act
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100127
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Actins)
RN  - 0 (Ccr7 protein, mouse)
RN  - 0 (Receptors, CCR7)
RN  - EC 3.1.4.3 (Phospholipase C gamma)
SB  - IM
MH  - Actins/*metabolism
MH  - Animals
MH  - Arthritis/*enzymology/pathology
MH  - Dendritic Cells/immunology/*metabolism
MH  - *Disease Models, Animal
MH  - Fluorescent Antibody Technique
MH  - Lymphocyte Activation
MH  - Mice
MH  - Mice, Knockout
MH  - Phospholipase C gamma/genetics/*metabolism
MH  - Receptors, CCR7/metabolism
MH  - Signal Transduction
PMC - PMC2811739
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2010/01/30 06:00
MHDA- 2010/05/21 06:00
PMCR- 2010/01/27
CRDT- 2010/01/30 06:00
PHST- 2009/06/19 00:00 [received]
PHST- 2009/10/13 00:00 [accepted]
PHST- 2010/01/30 06:00 [entrez]
PHST- 2010/01/30 06:00 [pubmed]
PHST- 2010/05/21 06:00 [medline]
PHST- 2010/01/27 00:00 [pmc-release]
AID - 09-PONE-RA-11145R1 [pii]
AID - 10.1371/journal.pone.0008909 [doi]
PST - epublish
SO  - PLoS One. 2010 Jan 27;5(1):e8909. doi: 10.1371/journal.pone.0008909.