PMID- 21357539
OWN - NLM
STAT- MEDLINE
DCOM- 20110616
LR  - 20110322
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 186
IP  - 7
DP  - 2011 Apr 1
TI  - The phosphatase SRC homology region 2 domain-containing phosphatase-1 is an 
      intrinsic central regulator of dendritic cell function.
PG  - 3934-45
LID - 10.4049/jimmunol.1001675 [doi]
AB  - Dendritic cells (DCs) initiate proinflammatory or regulatory T cell responses, 
      depending on their activation state. Despite extensive knowledge of DC-activating 
      signals, the understanding of DC inhibitory signals is relatively limited. We 
      show that Src homology region 2 domain-containing phosphatase-1 (SHP-1) is an 
      important inhibitor of DC signaling, targeting multiple activation pathways. 
      Downstream of TLR4, SHP-1 showed increased interaction with several proteins 
      including IL-1R-associated kinase-4, and modulated LPS signaling by inhibiting 
      NF-kappaB, AP-1, ERK, and JNK activity, while enhancing p38 activity. In addition, 
      SHP-1 inhibited prosurvival signaling through AKT activation. Furthermore, SHP-1 
      inhibited CCR7 protein expression. Inhibiting SHP-1 in DCs enhanced 
      proinflammatory cytokines, IL-6, IL-12, and IL-1beta production, promoted survival, 
      and increased DC migration to draining lymph nodes. Administration of 
      SHP-1-inhibited DCs in vivo induced expansion of Ag-specific cytotoxic T cells 
      and inhibited Foxp3(+) regulatory T cell induction, resulting in an enhanced 
      immune response against pre-established mouse melanoma and prostate tumors. Taken 
      together, these data demonstrate that SHP-1 is an intrinsic global regulator of 
      DC function, controlling many facets of T cell-mediated immune responses.
FAU - Ramachandran, Indu R
AU  - Ramachandran IR
AD  - Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 
      77030, USA.
FAU - Song, Weitao
AU  - Song W
FAU - Lapteva, Natalia
AU  - Lapteva N
FAU - Seethammagari, Mamatha
AU  - Seethammagari M
FAU - Slawin, Kevin M
AU  - Slawin KM
FAU - Spencer, David M
AU  - Spencer DM
FAU - Levitt, Jonathan M
AU  - Levitt JM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20110225
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (NF-kappa B)
RN  - 0 (Transcription Factor AP-1)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 6)
RN  - EC 3.1.3.48 (Ptpn6 protein, mouse)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Cell Line, Tumor
MH  - Cells, Cultured
MH  - Dendritic Cells/*enzymology/*immunology/metabolism
MH  - HEK293 Cells
MH  - Humans
MH  - Male
MH  - Melanoma, Experimental
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - NF-kappa B/antagonists & inhibitors/metabolism
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 6/*physiology
MH  - Signal Transduction/genetics/immunology
MH  - Transcription Factor AP-1/antagonists & inhibitors/metabolism
MH  - Transcriptional Activation/immunology
EDAT- 2011/03/02 06:00
MHDA- 2011/06/17 06:00
CRDT- 2011/03/02 06:00
PHST- 2011/03/02 06:00 [entrez]
PHST- 2011/03/02 06:00 [pubmed]
PHST- 2011/06/17 06:00 [medline]
AID - jimmunol.1001675 [pii]
AID - 10.4049/jimmunol.1001675 [doi]
PST - ppublish
SO  - J Immunol. 2011 Apr 1;186(7):3934-45. doi: 10.4049/jimmunol.1001675. Epub 2011 
      Feb 25.