Source:http://linkedlifedata.com/resource/pubmed/id/15802534
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rdf:type | |
lifeskim:mentions |
umls-concept:C0019796,
umls-concept:C0030685,
umls-concept:C0036536,
umls-concept:C0036537,
umls-concept:C0332283,
umls-concept:C0383327,
umls-concept:C0391871,
umls-concept:C0680255,
umls-concept:C0682685,
umls-concept:C1155064,
umls-concept:C1254042,
umls-concept:C1274040,
umls-concept:C1283071,
umls-concept:C1333908,
umls-concept:C1521761,
umls-concept:C1704675,
umls-concept:C1963578
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pubmed:issue |
2
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pubmed:dateCreated |
2005-7-4
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pubmed:abstractText |
Interaction of natural killer (NK) cells with autologous immature dendritic cells (DCs) results in reciprocal activation; however, the underlying mechanisms are so far elusive. We show here that NK cells trigger immature DCs to polarize and secrete interleukin 18 (IL-18), a cytokine lacking a secretory leader sequence. This occurs through a Ca2+-dependent and tubulin-mediated recruitment of IL-18-containing secretory lysosomes toward the adhering NK cell. Lysosome exocytosis and IL-18 secretion are restricted at the synaptic cleft, thus allowing activation of the interacting NK cells without spreading of the cytokine. In turn, DC-activated NK cells secrete the proinflammatory cytokine high mobility group B1 (HMGB1), which induces DC maturation and protects DCs from lysis. Also HMGB1 is a leaderless cytokine that undergoes regulated secretion. Differently from IL-18, soluble HMGB1 is consistently detected in NK/DC supernatants. These data point to secretion of leaderless cytokines as a key event for the reciprocal activation of NK cells and DCs. DCs initiate NK cell activation by targeted delivery of IL-18, thus instructing NK cells in the absence of adaptive-type cytokines; in turn, activated NK cells release HMGB1, which promotes inflammation and induces DC maturation, thus favoring the onset of the adaptive immune response.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/HMGB1 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-18,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tubulin
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0006-4971
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
106
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
609-16
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:15802534-Calcium Signaling,
pubmed-meshheading:15802534-Cell Communication,
pubmed-meshheading:15802534-Cell Differentiation,
pubmed-meshheading:15802534-Cell Polarity,
pubmed-meshheading:15802534-Cytokines,
pubmed-meshheading:15802534-Cytotoxicity, Immunologic,
pubmed-meshheading:15802534-Dendritic Cells,
pubmed-meshheading:15802534-HMGB1 Protein,
pubmed-meshheading:15802534-Humans,
pubmed-meshheading:15802534-Interleukin-18,
pubmed-meshheading:15802534-Killer Cells, Natural,
pubmed-meshheading:15802534-Recombinant Proteins,
pubmed-meshheading:15802534-Tubulin
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pubmed:year |
2005
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pubmed:articleTitle |
NK/iDC interaction results in IL-18 secretion by DCs at the synaptic cleft followed by NK cell activation and release of the DC maturation factor HMGB1.
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pubmed:affiliation |
Laboratory of Cell Biology, Department of Translational Oncology, National Institute for Cancer Research, Largo Rosanna Benzi, 10, 16132 Genova, Italy.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't
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