Dendritic cells release HLA-B-associated transcript-3 positive exosomes to regulate natural killer function.
NKp30, a natural cytotoxicity receptor expressed on NK cells is critically involved in direct cytotoxicity against various tumor cells and directs both maturation and selective killing of dendritic cells. Recently the intracellular protein BAT3, which is involved in DNA damage induced apoptosis, was identified as a ligand for NKp30. However, the mechanisms underlying the exposure of the intracellular ligand BAT3 to surface NKp30 and its role in NK-DC cross talk remained elusive. Electron microscopy and flow cytometry demonstrate that exosomes released from 293T cells and iDCs express BAT3 on the surface and are recognized by NKp30-Ig. Overexpression and depletion of BAT3 in 293T cells directly correlates with the exosomal expression level and the activation of NK cell-mediated cytokine release. Furthermore, the NKp30-mediated NK/DC cross talk resulting either in iDC killing or maturation was BAT3-dependent. Taken together this puts forward a new model for the activation of NK cells through intracellular signals that are released via exosomes from accessory cells. The manipulation of the exosomal regulation may offer a novel strategy to induce tumor immunity or inhibit autoimmune diseases caused by NK cell-activation.
Laboratory of Immune Therapy, Department of Internal Medicine I, Centre for Integrated Oncology Koeln Bonn, University of Cologne, Cologne, Germany. venkatsimhadri@googlemail.com
Venkateswara Rao
VR
Simhadri
Katrin S
KS
Reiners
Hinrich P
HP
Hansen
Daniela
D
Topolar
Vijaya Lakshmi
VL
Simhadri
Klaus
K
Nohroudi
Thomas A
TA
Kufer
Andreas
A
Engert
Elke
E
Pogge von Strandmann
D002460:Cell Line; D003713:Dendritic Cells / Q000378:metabolism* / Q000648:ultrastructure; D055354:Exosomes / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D007694:Killer Cells, Natural / Q000737:chemistry / Q000276:immunology*; D008024:Ligands; D008854:Microscopy, Electron; D018832:Molecular Chaperones; D055628:Natural Cytotoxicity Triggering Receptor 3 / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*
C092009:BAG6 protein, human; D008024:Ligands; D018832:Molecular Chaperones; C431710:NCR3 protein, human; D055628:Natural Cytotoxicity Triggering Receptor 3; D011506:Proteins