| First Author | Kasamatsu J | Year | 2014 |
| Journal | J Immunol | Volume | 193 |
| Issue | 10 | Pages | 5199-207 |
| PubMed ID | 25320282 | Mgi Jnum | J:260677 |
| Mgi Id | MGI:6152544 | Doi | 10.4049/jimmunol.1400924 |
| Citation | Kasamatsu J, et al. (2014) INAM plays a critical role in IFN-gamma production by NK cells interacting with polyinosinic-polycytidylic acid-stimulated accessory cells. J Immunol 193(10):5199-207 |
| abstractText | Polyinosinic-polycytidylic acid strongly promotes the antitumor activity of NK cells via TLR3/Toll/IL-1R domain-containing adaptor molecule 1 and melanoma differentiation-associated protein-5/mitochondrial antiviral signaling protein pathways. Polyinosinic-polycytidylic acid acts on accessory cells such as dendritic cells (DCs) and macrophages (Mphis) to secondarily activate NK cells. In a previous study in this context, we identified a novel NK-activating molecule, named IFN regulatory factor 3-dependent NK-activating molecule (INAM), a tetraspanin-like membrane glycoprotein (also called Fam26F). In the current study, we generated INAM-deficient mice and investigated the in vivo function of INAM. We found that cytotoxicity against NK cell-sensitive tumor cell lines was barely decreased in Inam(-/-) mice, whereas the number of IFN-gamma-producing cells was markedly decreased in the early phase. Notably, deficiency of INAM in NK and accessory cells, such as CD8alpha(+) conventional DCs and Mphis, led to a robust decrease in IFN-gamma production. In conformity with this phenotype, INAM effectively suppressed lung metastasis of B16F10 melanoma cells, which is controlled by NK1.1(+) cells and IFN-gamma. These results suggest that INAM plays a critical role in NK-CD8alpha(+) conventional DC (and Mphi) interaction leading to IFN-gamma production from NK cells in vivo. INAM could therefore be a novel target molecule for cancer immunotherapy against IFN-gamma-suppressible metastasis. |
