Linked Life Data

21357539

Source:http://linkedlifedata.com/resource/pubmed/id/21357539

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2011-3-22
pubmed:abstractText
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-?B, 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-1? 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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1550-6606
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
186
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3934-45
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
The phosphatase SRC homology region 2 domain-containing phosphatase-1 is an intrinsic central regulator of dendritic cell function.
pubmed:affiliation
Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't