INAM plays a critical role in IFN-γ production by NK cells interacting with polyinosinic-polycytidylic acid-stimulated accessory cells

Jun Kasamatsu, Masahiro Azuma, Hiroyuki Oshiumi, Yuka Morioka, Masaru Okabe, Takashi Ebihara, Misako Matsumoto, Tsukasa Seya

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Polyinosinic-polycytidylic acid strongly promotes the antitumor activity ofNKcells via TLR3/Toll/IL-1R domain-containing adaptor molecule 1 and melanoma differentiation-associated protein-5/mitochondrial antiviral signaling protein pathways. Polyinosinicpolycytidylic acid acts on accessory cells such as dendritic cells (DCs) and macrophages (Mφs) 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 NKactivating 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-γ-producing cells was markedly decreased in the early phase. Notably, deficiency of INAM in NK and accessory cells, such as CD8α+ conventional DCs and Mφs, led to a robust decrease in IFN-γ production. In conformity with this phenotype, INAM effectively suppressed lung metastasis of B16F10 melanoma cells, which is controlled by NK1.1+ cells and IFN-γ. These results suggest that INAM plays a critical role in NK-CD8α+ conventional DC (and Mφ) interaction leading to IFN-γ production from NK cells in vivo. INAM could therefore be a novel target molecule for cancer immunotherapy against IFN-γ-suppressible metastasis.

Original languageEnglish
Pages (from-to)5199-5207
Number of pages9
JournalJournal of Immunology
Volume193
Issue number10
DOIs
Publication statusPublished - 2014 Nov 15

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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