PMID- 21755007
OWN - NLM
STAT- MEDLINE
DCOM- 20111109
LR  - 20211203
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 6
IP  - 7
DP  - 2011
TI  - SHIP-deficient dendritic cells, unlike wild type dendritic cells, suppress T cell 
      proliferation via a nitric oxide-independent mechanism.
PG  - e21893
LID - 10.1371/journal.pone.0021893 [doi]
LID - e21893
AB  - BACKGROUND: Dendritic cells (DCs) not only play a crucial role in activating 
      immune cells but also suppressing them. We recently investigated SHIP's role in 
      murine DCs in terms of immune cell activation and found that TLR 
      agonist-stimulated SHIP-/- GM-CSF-derived DCs (GM-DCs) were far less capable than 
      wild type (WT, SHIP+/+) GM-DCs at activating T cell proliferation. This was most 
      likely because SHIP-/- GM-DCs could not up-regulate MHCII and/or co-stimulatory 
      receptors following TLR stimulation. However, the role of SHIP in DC-induced T 
      cell suppression was not investigated. METHODOLOGY/PRINCIPAL FINDINGS: In this 
      study we examined SHIP's role in DC-induced T cell suppression by co-culturing WT 
      and SHIP-/- murine DCs, derived under different conditions or isolated from 
      spleens, with alphaCD3+ alphaCD28 activated WT T cells and determined the relative 
      suppressive abilities of the different DC subsets. We found that, in contrast to 
      SHIP+/+ and -/- splenic or Flt3L-derived DCs, which do not suppress T cell 
      proliferation in vitro, both SHIP+/+ and -/- GM-DCs were capable of potently 
      suppressing T cell proliferation. However, WT GM-DC suppression appeared to be 
      mediated, at least in part, by nitric oxide (NO) production while SHIP-/- GM-DCs 
      expressed high levels of arginase 1 and did not produce NO. Following exhaustive 
      studies to ascertain the mechanism of SHIP-/- DC-mediated suppression, we could 
      conclude that cell-cell contact was required and the mechanism may be related to 
      their relative immaturity, compared to SHIP+/+ GM-DCs. CONCLUSIONS: These 
      findings suggest that although both SHIP+/+ and -/- GM-DCs suppress T cell 
      proliferation, the mechanism(s) employed are different. WT GM-DCs suppress, at 
      least in part, via IFNgamma-induced NO production while SHIP-/- GM-DCs do not produce 
      NO and suppression can only be alleviated when contact is prevented.
FAU - Antignano, Frann
AU  - Antignano F
AD  - The Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British 
      Columbia, Canada.
FAU - Hamilton, Melisa
AU  - Hamilton M
FAU - Patterson, Scott
AU  - Patterson S
FAU - Ho, Victor
AU  - Ho V
FAU - Cohen, Carla
AU  - Cohen C
FAU - Levings, Megan K
AU  - Levings MK
FAU - Krystal, Gerald
AU  - Krystal G
LA  - eng
GR  - MOP 57834/Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110706
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Amino Acids)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
RN  - EC 3.1.3.2 (Phosphoric Monoester Hydrolases)
RN  - EC 3.1.3.56 (Inositol Polyphosphate 5-Phosphatases)
RN  - EC 3.5.3.1 (Arginase)
SB  - IM
MH  - Amino Acids/metabolism
MH  - Animals
MH  - Arginase/metabolism
MH  - Cell Adhesion/drug effects
MH  - Cell Proliferation/drug effects
MH  - Coculture Techniques
MH  - Dendritic Cells/*cytology/drug effects/enzymology
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology
MH  - Immunosuppression Therapy
MH  - Inositol Polyphosphate 5-Phosphatases
MH  - Interferon-gamma/metabolism
MH  - Lymphocyte Activation/drug effects
MH  - Mice
MH  - Models, Immunological
MH  - Nitric Oxide/metabolism
MH  - Phosphoric Monoester Hydrolases/*deficiency/metabolism
MH  - T-Lymphocytes/*cytology/drug effects/immunology
PMC - PMC3130768
COIS- Competing Interests: GK is a founding member of Aquinox Pharmaceuticals Inc, 
      which is dedicated to identifying small molecule activators and inhibitors of 
      SHIP, however, none were used in this study. In addition, no compensation is 
      received for being a founder of Aquinox and GK is not currently a consultant or 
      an employee of Aquinox. There are no patents, products in development or marketed 
      products to declare. This does not alter the authors' adherence to all the PLoS 
      ONE policies on sharing data and materials, as detailed online in the guide for 
      authors.
EDAT- 2011/07/15 06:00
MHDA- 2011/11/10 06:00
PMCR- 2011/07/06
CRDT- 2011/07/15 06:00
PHST- 2011/03/30 00:00 [received]
PHST- 2011/06/07 00:00 [accepted]
PHST- 2011/07/15 06:00 [entrez]
PHST- 2011/07/15 06:00 [pubmed]
PHST- 2011/11/10 06:00 [medline]
PHST- 2011/07/06 00:00 [pmc-release]
AID - PONE-D-11-05952 [pii]
AID - 10.1371/journal.pone.0021893 [doi]
PST - ppublish
SO  - PLoS One. 2011;6(7):e21893. doi: 10.1371/journal.pone.0021893. Epub 2011 Jul 6.