Gap junction intercellular communications regulate NK cell activation and modulate NK cytotoxic capacity
Author
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Tittarelli, Andrés
Author
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Mendoza Naranjo, Ariadna
es_CL
Author
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Farías, Marcela
es_CL
Author
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Guerrero, Israel
es_CL
Author
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Ihara, Fumitaka
es_CL
Author
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Wennerberg, Erik
es_CL
Author
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Riquelme, Sebastián
es_CL
Author
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Gleisner, Alejandra
es_CL
Author
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Kalergis, Alexis
es_CL
Author
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Lundqvist, Andreas
es_CL
Author
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López Nitsche, Mercedes
es_CL
Author
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Chambers, Benedict J.
es_CL
Author
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Salazar Onfray, Flavio
es_CL
Admission date
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2015-01-09T13:10:28Z
Available date
dc.date.available
2015-01-09T13:10:28Z
Publication date
dc.date.issued
2014
Cita de ítem
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J Immunol 2014; 192:1313-1319
en_US
Identifier
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DOI: 10.4049/jimmunol.1301297
Identifier
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https://repositorio.uchile.cl/handle/2250/129623
General note
dc.description
Artículo de publicación ISI
en_US
Abstract
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Gap junctions (GJs) mediate intercellular communication between adjacent cells. Previously, we showed that connexin 43 (Cx43),
the main GJ protein in the immune system, mediates Ag transfer between human dendritic cells (DCs) and is recruited to the
immunological synapse during T cell priming. This crosstalk contributed to T cell activation, intracellular Ca2+ responses, and
cytokine release. However, the role of GJs in NK cell activation by DCs and NK cell–mediated cytotoxicity against tumor cells
remains unknown. In this study, we found polarization of Cx43 at the NK/DC and NK/tumor cell-contact sites, accompanied by
the formation of functional GJs between NK/DCs and NK/tumor cells, respectively. Cx43–GJ-mediated intercellular communication
(GJIC) between human NK and DCs was bidirectional. Blockage of Cx43-GJIC inhibited NK cell activation, though it
affected neither the phenotype nor the function of DCs. Cx43 knockdown or inhibition using mimetic peptides greatly reduced
CD69 and CD25 expression and IFN-g release by DC-stimulated NK cells. Moreover, blocking Cx43 strongly inhibited the NK
cell–mediated tumor cell lysis associated with inhibition of granzyme B activity and Ca2+ influx. Our data identify a novel and
active role for Cx43-GJIC in human NK cell activation and antitumor effector functions that may be important for the design of
new immune therapeutic strategies.