PMID- 17164346 OWN - NLM STAT- MEDLINE DCOM- 20070523 LR - 20210206 IS - 0006-4971 (Print) IS - 1528-0020 (Electronic) IS - 0006-4971 (Linking) VI - 109 IP - 8 DP - 2007 Apr 15 TI - Essential role of the TNF-TNFR2 cognate interaction in mouse dendritic cell-natural killer cell crosstalk. PG - 3333-41 AB - Dendritic cells (DCs) and natural killer (NK) cells are essential components of the innate immune system and have a central role in initiation and regulation of adaptive immune responses. During the early critical immune activities, DCs and NK cells interact and reciprocally regulate each other via cell-cell contact. The molecular mediators of the DC-NK-cell crosstalk are largely undefined. In the present study, we show in mice that DC stimulation of NK-cell IFN-gamma secretion requires DC membrane-bound but not secreted products; is increased by augmenting the expression of DC transmembrane tumor necrosis factor (tmTNF) and NK-cell transmembrane TNF receptor type 2 (tmTNFR2); is inhibited by blocking TNF or TNFR2 but not TNFR1; is impaired by knocking out DC Tnf or NK-cell Tnfr2 but not DC Tnfr1 or Tnfr2 and NK-cell Tnf or Tnfr1; and is restored in TNF-deficient DCs by reconstituting tmTNF, but cannot be mimicked by soluble TNF. We also demonstrate that DC TNF and NK-cell TNFR2 are required for DC-mediated NK-cell proliferation and amplification of cytotoxic activity. These novel findings provide the first evidence that DC-NK-cell crosstalk mediates enhancement of NK-cell functions via triggering NK-cell tmTNFR2 by DC tmTNF. FAU - Xu, Jun AU - Xu J AD - University of Pittsburgh Cancer Institute, Hillman Cancer Center, 5117 Centre Avenue, Pittsburgh, PA, USA. FAU - Chakrabarti, Ayan K AU - Chakrabarti AK FAU - Tan, Jennifer L AU - Tan JL FAU - Ge, Lisheng AU - Ge L FAU - Gambotto, Andrea AU - Gambotto A FAU - Vujanovic, Nikola L AU - Vujanovic NL LA - eng GR - P60 DE013059/DE/NIDCR NIH HHS/United States GR - R01 DE014775/DE/NIDCR NIH HHS/United States GR - 1P0 DE 13059/DE/NIDCR NIH HHS/United States GR - R01 DE 14775/DE/NIDCR NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20061212 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Antiviral Agents) RN - 0 (Receptors, Tumor Necrosis Factor, Type I) RN - 0 (Receptors, Tumor Necrosis Factor, Type II) RN - 0 (Tnfrsf1a protein, mouse) RN - 0 (Tumor Necrosis Factors) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Animals MH - Antiviral Agents/immunology/pharmacology MH - Cell Communication/drug effects/*immunology MH - *Cell Proliferation/drug effects MH - Cells, Cultured MH - Coculture Techniques MH - Dendritic Cells/*immunology MH - Female MH - Interferon-gamma/immunology/pharmacology MH - Killer Cells, Natural/*immunology MH - Mice MH - Mice, Knockout MH - Receptors, Tumor Necrosis Factor, Type I/immunology MH - Receptors, Tumor Necrosis Factor, Type II/*immunology MH - Tumor Necrosis Factors/*immunology PMC - PMC1852244 EDAT- 2006/12/14 09:00 MHDA- 2007/05/24 09:00 PMCR- 2008/04/15 CRDT- 2006/12/14 09:00 PHST- 2006/12/14 09:00 [pubmed] PHST- 2007/05/24 09:00 [medline] PHST- 2006/12/14 09:00 [entrez] PHST- 2008/04/15 00:00 [pmc-release] AID - S0006-4971(20)41708-2 [pii] AID - 2006/026385 [pii] AID - 10.1182/blood-2006-06-026385 [doi] PST - ppublish SO - Blood. 2007 Apr 15;109(8):3333-41. doi: 10.1182/blood-2006-06-026385. Epub 2006 Dec 12.