dendritic cells release hla-b-associated transcript-3 positive exosomes to regulate natural killer function树突细胞释放hla-b-associated transcript-3积极液调节自然杀伤功能.pdfVIP

Dendritic Cells Release HLA-B-Associated Transcript-3 Positive Exosomes to Regulate Natural Killer Function 1 1 1 1 Venkateswara Rao Simhadri *, Katrin S. Reiners , Hinrich P. Hansen , Daniela Topolar , Vijaya Lakshmi 1 2 3 1 1 Simhadri , Klaus Nohroudi , Thomas A. Kufer , Andreas Engert , Elke Pogge von Strandmann * 1 Laboratory of Immune Therapy, Department of Internal Medicine I, Centre for Integrated Oncology Koeln Bonn, University of Cologne, Cologne, Germany, 2 Institute for Anatomy-I, University Hospital of Cologne, Cologne, Germany, 3 Institute of Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany Abstract 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 a