| First Author | Xu J | Year | 2007 |
| Journal | Blood | Volume | 109 |
| Issue | 8 | Pages | 3333-41 |
| PubMed ID | 17164346 | Mgi Jnum | J:145343 |
| Mgi Id | MGI:3834328 | Doi | 10.1182/blood-2006-06-026385 |
| Citation | Xu J, et al. (2007) Essential role of the TNF-TNFR2 cognate interaction in mouse dendritic cell-natural killer cell crosstalk. Blood 109(8):3333-41 |
| abstractText | 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. |
